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KLF1 - Revision history
2024-03-28T15:00:00Z
Revision history for this page on the wiki
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imported>Boghog: consistent citation formatting
2018-10-24T15:39:39Z
<p>consistent citation formatting</p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 15:39, 24 October 2018</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Structure ==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Structure ==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The molecule has two domains; the [[Transcription factor#Trans-activating domain|transactivation domain]] and the [[chromatin]]-remodeling domain. The carboxyl (C) terminal is composed of three C2H2 [[zinc finger]]s that binds to DNA, and the amino (N) terminus is proline rich and acidic.<ref name="pmid11739731">{{cite journal |vauthors=Brown RC, Pattison S, van Ree J, Coghill E, Perkins A, Jane SM, Cunningham JM | title = Distinct domains of erythroid Krüppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter | journal = <del style="font-weight: bold; text-decoration: none;">Mol. Cell. Biol. </del>| volume = 22 | issue = 1 | pages = 161–70 |date=January 2002 | pmid = 11739731 | pmc = 134232 | doi = 10.1128/mcb.22.1.161-170.2002}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The molecule has two domains; the [[Transcription factor#Trans-activating domain|transactivation domain]] and the [[chromatin]]-remodeling domain. The carboxyl (C) terminal is composed of three C2H2 [[zinc finger]]s that binds to DNA, and the amino (N) terminus is proline rich and acidic.<ref name="pmid11739731">{{cite journal | vauthors = Brown RC, Pattison S, van Ree J, Coghill E, Perkins A, Jane SM, Cunningham JM | title = Distinct domains of erythroid Krüppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter | journal = <ins style="font-weight: bold; text-decoration: none;">Molecular and Cellular Biology </ins>| volume = 22 | issue = 1 | pages = 161–70 | date = January 2002 | pmid = 11739731 | pmc = 134232 | doi = 10.1128/mcb.22.1.161-170.2002 }}</ref></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Function ==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Function ==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Studies in mice first demonstrated the critical function of KLF1 in hematopoietic development. KLF1 deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult β-globin, and die by embryonic day 15.<ref name="Perkins et al">{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Perkins<del style="font-weight: bold; text-decoration: none;">|first1=Andrew|last2=</del>Sharpe<del style="font-weight: bold; text-decoration: none;">|first2=Ariene|last3=</del>Orkin<del style="font-weight: bold; text-decoration: none;">|first3=Stuart</del>|title=Lethal <del style="font-weight: bold; text-decoration: none;">β</del>-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF<del style="font-weight: bold; text-decoration: none;">.</del>|journal=Nature<del style="font-weight: bold; text-decoration: none;">|date=1995</del>|volume=375|issue=6529|pages=<del style="font-weight: bold; text-decoration: none;">318–322</del>|doi=10.1038/375318a0<del style="font-weight: bold; text-decoration: none;">|pmid=7753195</del>}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Studies in mice first demonstrated the critical function of KLF1 in hematopoietic development. KLF1 deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult β-globin, and die by embryonic day 15.<ref name="Perkins et al">{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Perkins <ins style="font-weight: bold; text-decoration: none;">AC, </ins>Sharpe <ins style="font-weight: bold; text-decoration: none;">AH, </ins>Orkin <ins style="font-weight: bold; text-decoration: none;">SH </ins>| title = Lethal <ins style="font-weight: bold; text-decoration: none;">beta</ins>-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF | journal = Nature | volume = 375 | issue = 6529 | pages = <ins style="font-weight: bold; text-decoration: none;">318–22 | date = May 1995 | pmid = 7753195 </ins>| doi = 10.1038/375318a0 }}</ref></div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Over-expression of KLF1 results in a reduction of the number of circulating platelets and hastens the onset of the β-globin gene.<ref>{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Tewari<del style="font-weight: bold; text-decoration: none;">|first1=Rita|last2=</del>Gillemans<del style="font-weight: bold; text-decoration: none;">|first2=Nynke|last3=</del>Wijgerde<del style="font-weight: bold; text-decoration: none;">|first3=Mark|last4=</del>Nuez<del style="font-weight: bold; text-decoration: none;">|first4=Beatriz|last5=</del>von Lindern<del style="font-weight: bold; text-decoration: none;">|first5=Marieke|last6=</del>Grosveld<del style="font-weight: bold; text-decoration: none;">|first6=Frank|last7=</del>Philipsen<del style="font-weight: bold; text-decoration: none;">|first7=Sjaak</del>|title=Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5 HS3 of the <del style="font-weight: bold; text-decoration: none;">β</del>-globin locus control region|journal=EMBO <del style="font-weight: bold; text-decoration: none;">J|date=1998</del>|volume=17|issue=8|pages=<del style="font-weight: bold; text-decoration: none;">2334–2341</del>|doi=10.1093/emboj/17.8.2334<del style="font-weight: bold; text-decoration: none;">|pmid=9545245</del>}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Over-expression of KLF1 results in a reduction of the number of circulating platelets and hastens the onset of the β-globin gene.<ref>{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Tewari <ins style="font-weight: bold; text-decoration: none;">R, </ins>Gillemans <ins style="font-weight: bold; text-decoration: none;">N, </ins>Wijgerde <ins style="font-weight: bold; text-decoration: none;">M, </ins>Nuez <ins style="font-weight: bold; text-decoration: none;">B, </ins>von Lindern <ins style="font-weight: bold; text-decoration: none;">M, </ins>Grosveld <ins style="font-weight: bold; text-decoration: none;">F, </ins>Philipsen <ins style="font-weight: bold; text-decoration: none;">S </ins>| title = Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5<ins style="font-weight: bold; text-decoration: none;">'</ins>HS3 of the <ins style="font-weight: bold; text-decoration: none;">beta</ins>-globin locus control region | journal = <ins style="font-weight: bold; text-decoration: none;">The </ins>EMBO <ins style="font-weight: bold; text-decoration: none;">Journal </ins>| volume = 17 | issue = 8 | pages = <ins style="font-weight: bold; text-decoration: none;">2334–41 | date = April 1998 | pmid = 9545245 | pmc = 1170576 </ins>| doi = 10.1093/emboj/17.8.2334 }}</ref></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>KLF1 coordinates the regulation of six cellular pathways that are all essential to terminal erythroid differentiation:<ref>{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Tallack<del style="font-weight: bold; text-decoration: none;">|first1=Michael|last2=</del>Perkins<del style="font-weight: bold; text-decoration: none;">|first2=Andrew</del>|title=KLF1 <del style="font-weight: bold; text-decoration: none;">Directly Coordinates Almost All Aspects </del>of <del style="font-weight: bold; text-decoration: none;">Terminal Erythroid Differentiation</del>|journal=IUBMB Life<del style="font-weight: bold; text-decoration: none;">|date=2010</del>|volume=62|issue=12|pages=<del style="font-weight: bold; text-decoration: none;">886–890</del>|doi=10.1002/iub.404<del style="font-weight: bold; text-decoration: none;">|pmid=21190291</del>}}</ref></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>KLF1 coordinates the regulation of six cellular pathways that are all essential to terminal erythroid differentiation:<ref>{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Tallack <ins style="font-weight: bold; text-decoration: none;">MR, </ins>Perkins <ins style="font-weight: bold; text-decoration: none;">AC </ins>| title = KLF1 <ins style="font-weight: bold; text-decoration: none;">directly coordinates almost all aspects </ins>of <ins style="font-weight: bold; text-decoration: none;">terminal erythroid differentiation </ins>| journal = IUBMB Life | volume = 62 | issue = 12 | pages = <ins style="font-weight: bold; text-decoration: none;">886–90 | date = December 2010 | pmid = 21190291 </ins>| doi = 10.1002/iub.404 }}</ref></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div># Cell Membrane & Cytoskeleton</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div># Cell Membrane & Cytoskeleton</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Clinical significance ==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== Clinical significance ==</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Next-Generation sequencing efforts have revealed a surprisingly high prevalence of mutations in human KLF1. The chance of a KLF1 null child being conceived is approximately 1:24,000 in Southern China.<ref name="Perkins review">{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Perkins<del style="font-weight: bold; text-decoration: none;">|first1=Andrew|last2=</del>Xu<del style="font-weight: bold; text-decoration: none;">|first2=Xiangmin|last3=</del>Higgs<del style="font-weight: bold; text-decoration: none;">|first3=Douglas|last4=The KLF1 Consensus Workgroup|last5=</del>Patrinos<del style="font-weight: bold; text-decoration: none;">|first5=George|last6=</del>Arnaud<del style="font-weight: bold; text-decoration: none;">|first6=Lionel|last7=</del>Bieker<del style="font-weight: bold; text-decoration: none;">|first7=James|last8=</del>Philipsen<del style="font-weight: bold; text-decoration: none;">|first8=Sjaak</del>|title=Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants<del style="font-weight: bold; text-decoration: none;">.</del>|journal=Blood<del style="font-weight: bold; text-decoration: none;">|date=2016</del>|volume=127|issue=15|pages=<del style="font-weight: bold; text-decoration: none;">1856–1862</del>|doi=10.1182/blood-2016-01-694331|<del style="font-weight: bold; text-decoration: none;">pmid</del>=<del style="font-weight: bold; text-decoration: none;">26903544</del>}}</ref> With pre-natal blood transfusions and bone marrow transplant, it is possible to be born without KLF1.<ref>{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Magor<del style="font-weight: bold; text-decoration: none;">|first1=Graham|last2=</del>Tallack<del style="font-weight: bold; text-decoration: none;">|first2=Michael|last3=</del>Gillinder<del style="font-weight: bold; text-decoration: none;">|first3=Kevin|last4=</del>Bell<del style="font-weight: bold; text-decoration: none;">|first4=Charles|last5=</del>McCallum<del style="font-weight: bold; text-decoration: none;">|first5=Naomi|last6=</del>Williams<del style="font-weight: bold; text-decoration: none;">|first6=Bronwyn|last7=</del>Perkins<del style="font-weight: bold; text-decoration: none;">|first7=Andrew</del>|title=KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome|journal=Blood<del style="font-weight: bold; text-decoration: none;">|date=2014</del>|volume=125|issue=15|pages=<del style="font-weight: bold; text-decoration: none;">2405–2417</del>|doi=10.1182/blood-2014-08-590968<del style="font-weight: bold; text-decoration: none;">|pmid=25724378</del>}}</ref> Most mutations in KLF1 lead to a recessive loss-of-function phenotype,<ref name="Perkins review" /> however semi-dominant mutations have been identified in humans<ref>{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Arnaud<del style="font-weight: bold; text-decoration: none;">|first1=Lionel|last2=</del>Saison<del style="font-weight: bold; text-decoration: none;">|first2=Carole|last3=</del>Helias<del style="font-weight: bold; text-decoration: none;">|first3=Virginie|last4=</del>Lucien<del style="font-weight: bold; text-decoration: none;">|first4=Nicole|last5=</del>Steschenko<del style="font-weight: bold; text-decoration: none;">|first5=Dominique|last6=</del>Giarratana<del style="font-weight: bold; text-decoration: none;">|first6=Marie-Catherine|last7=</del>Prehu<del style="font-weight: bold; text-decoration: none;">|first7=Claude|last8=</del>Foliguet<del style="font-weight: bold; text-decoration: none;">|first8=Bernard|last9=</del>Montout<del style="font-weight: bold; text-decoration: none;">|first9=Lory|last10=</del>de Brevern<del style="font-weight: bold; text-decoration: none;">|first10=Alexandre G.|last11=</del>Francina<del style="font-weight: bold; text-decoration: none;">|first11=Alain|last12=</del>Ripoche<del style="font-weight: bold; text-decoration: none;">|first12=Pierre|last13=</del>Fenneteau<del style="font-weight: bold; text-decoration: none;">|first13=Odile|last14=</del>Da Costa<del style="font-weight: bold; text-decoration: none;">|first14=Lydie|last15=</del>Peyrard<del style="font-weight: bold; text-decoration: none;">|first15=Thierry|last16=</del>Coghlan<del style="font-weight: bold; text-decoration: none;">|first16=Gail|last17=</del>Illum<del style="font-weight: bold; text-decoration: none;">|first17=Niels|last18=</del>Birgens<del style="font-weight: bold; text-decoration: none;">|first18=Henrik|last19=</del>Tamary<del style="font-weight: bold; text-decoration: none;">|first19=Hannah|last20=</del>Iolascon<del style="font-weight: bold; text-decoration: none;">|first20=Achille|last21=</del>Delaunay<del style="font-weight: bold; text-decoration: none;">|first21=Jean|last22=</del>Tchernia<del style="font-weight: bold; text-decoration: none;">|first22=Gil|last23=</del>Cartron<del style="font-weight: bold; text-decoration: none;">|first23=Jean-Pierre</del>|title=A <del style="font-weight: bold; text-decoration: none;">Dominant Mutation </del>in the <del style="font-weight: bold; text-decoration: none;">Gene Encoding </del>the <del style="font-weight: bold; text-decoration: none;">Erythroid Transcription Factor </del>KLF1 <del style="font-weight: bold; text-decoration: none;">Causes </del>a <del style="font-weight: bold; text-decoration: none;">Congenital Dyserythropoietic Anemia</del>|journal=<del style="font-weight: bold; text-decoration: none;">The </del>American Journal of Human Genetics<del style="font-weight: bold; text-decoration: none;">|date=2010</del>|volume=87|issue=5|pages=<del style="font-weight: bold; text-decoration: none;">721–727</del>|doi=10.1016/j.ajhg.2010.10.010}}</ref> and mice<ref>{{cite journal|<del style="font-weight: bold; text-decoration: none;">last1</del>=Gillinder<del style="font-weight: bold; text-decoration: none;">|first1=</del>KR<del style="font-weight: bold; text-decoration: none;">|last2=</del>Ilsley<del style="font-weight: bold; text-decoration: none;">|first2=</del>MD<del style="font-weight: bold; text-decoration: none;">|last3=</del>Nébor<del style="font-weight: bold; text-decoration: none;">|first3=</del>D<del style="font-weight: bold; text-decoration: none;">|last4=</del>Sachidanandam<del style="font-weight: bold; text-decoration: none;">|first4=</del>R<del style="font-weight: bold; text-decoration: none;">|last5=</del>Lajoie<del style="font-weight: bold; text-decoration: none;">|first5=</del>M<del style="font-weight: bold; text-decoration: none;">|last6=</del>Magor<del style="font-weight: bold; text-decoration: none;">|first6=</del>GW<del style="font-weight: bold; text-decoration: none;">|last7=</del>Tallack<del style="font-weight: bold; text-decoration: none;">|first7=</del>MR<del style="font-weight: bold; text-decoration: none;">|last8=</del>Bailey<del style="font-weight: bold; text-decoration: none;">|first8=</del>T<del style="font-weight: bold; text-decoration: none;">|last9=</del>Landsberg<del style="font-weight: bold; text-decoration: none;">|first9=</del>MJ<del style="font-weight: bold; text-decoration: none;">|last10=</del>Mackay<del style="font-weight: bold; text-decoration: none;">|first10=</del>JP<del style="font-weight: bold; text-decoration: none;">|last11=</del>Parker<del style="font-weight: bold; text-decoration: none;">|first11=</del>MW<del style="font-weight: bold; text-decoration: none;">|last12=</del>Miles<del style="font-weight: bold; text-decoration: none;">|first12=</del>LA<del style="font-weight: bold; text-decoration: none;">|last13=</del>Graber<del style="font-weight: bold; text-decoration: none;">|first13=</del>JH<del style="font-weight: bold; text-decoration: none;">|last14=</del>Peters<del style="font-weight: bold; text-decoration: none;">|first14=</del>LL<del style="font-weight: bold; text-decoration: none;">|last15=</del>Bieker<del style="font-weight: bold; text-decoration: none;">|first15=</del>JJ<del style="font-weight: bold; text-decoration: none;">|last16=</del>Perkins<del style="font-weight: bold; text-decoration: none;">|first16=</del>AC|title=Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability<del style="font-weight: bold; text-decoration: none;">.</del>|journal=Nucleic Acids Research|date=<del style="font-weight: bold; text-decoration: none;">2016</del>|doi=10.1093/nar/gkw1014<del style="font-weight: bold; text-decoration: none;">|pmid=27899603</del>}}</ref> as the cause of a rare inherited anemia [[Congenital dyserythropoietic anemia|CDA type IV]].</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Next-Generation sequencing efforts have revealed a surprisingly high prevalence of mutations in human KLF1.<ins style="font-weight: bold; text-decoration: none;"><ref>{{cite journal | vauthors = Gillinder K, Magor G, Perkins A | title = Variable serologic and other phenotypes due to KLF1 mutations | journal = Transfusion | volume = 58 | issue = 5 | pages = 1324–1325 | date = May 2018 | pmid = 29683509 | doi = 10.1111/trf.14529 }}</ref> </ins>The chance of a KLF1 null child being conceived is approximately 1:24,000 in Southern China.<ref name="Perkins review">{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Perkins <ins style="font-weight: bold; text-decoration: none;">A, </ins>Xu <ins style="font-weight: bold; text-decoration: none;">X, </ins>Higgs <ins style="font-weight: bold; text-decoration: none;">DR, </ins>Patrinos <ins style="font-weight: bold; text-decoration: none;">GP, </ins>Arnaud <ins style="font-weight: bold; text-decoration: none;">L, </ins>Bieker <ins style="font-weight: bold; text-decoration: none;">JJ, </ins>Philipsen <ins style="font-weight: bold; text-decoration: none;">S </ins>| title = Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants | journal = Blood | volume = 127 | issue = 15 | pages = <ins style="font-weight: bold; text-decoration: none;">1856–62 | date = April 2016 | pmid = 26903544 | pmc = 4832505 </ins>| doi = 10.1182/blood-2016-01-694331 | <ins style="font-weight: bold; text-decoration: none;">first8 = Sjaak | first5 = George | first6 = Lionel | first7 </ins>= <ins style="font-weight: bold; text-decoration: none;">James </ins>}}</ref> With pre-natal blood transfusions and bone marrow transplant, it is possible to be born without KLF1.<ref>{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Magor <ins style="font-weight: bold; text-decoration: none;">GW, </ins>Tallack <ins style="font-weight: bold; text-decoration: none;">MR, </ins>Gillinder <ins style="font-weight: bold; text-decoration: none;">KR, </ins>Bell <ins style="font-weight: bold; text-decoration: none;">CC, </ins>McCallum <ins style="font-weight: bold; text-decoration: none;">N, </ins>Williams <ins style="font-weight: bold; text-decoration: none;">B, </ins>Perkins <ins style="font-weight: bold; text-decoration: none;">AC </ins>| title = KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome | journal = Blood | volume = 125 | issue = 15 | pages = <ins style="font-weight: bold; text-decoration: none;">2405–17 | date = April 2015 | pmid = 25724378 | pmc = 4521397 </ins>| doi = 10.1182/blood-2014-08-590968 }}</ref> Most mutations in KLF1 lead to a recessive loss-of-function phenotype,<ref name="Perkins review" /> however semi-dominant mutations have been identified in humans<ref>{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Arnaud <ins style="font-weight: bold; text-decoration: none;">L, </ins>Saison <ins style="font-weight: bold; text-decoration: none;">C, </ins>Helias <ins style="font-weight: bold; text-decoration: none;">V, </ins>Lucien <ins style="font-weight: bold; text-decoration: none;">N, </ins>Steschenko <ins style="font-weight: bold; text-decoration: none;">D, </ins>Giarratana <ins style="font-weight: bold; text-decoration: none;">MC, </ins>Prehu <ins style="font-weight: bold; text-decoration: none;">C, </ins>Foliguet <ins style="font-weight: bold; text-decoration: none;">B, </ins>Montout <ins style="font-weight: bold; text-decoration: none;">L, </ins>de Brevern <ins style="font-weight: bold; text-decoration: none;">AG, </ins>Francina <ins style="font-weight: bold; text-decoration: none;">A, </ins>Ripoche <ins style="font-weight: bold; text-decoration: none;">P, </ins>Fenneteau <ins style="font-weight: bold; text-decoration: none;">O, </ins>Da Costa <ins style="font-weight: bold; text-decoration: none;">L, </ins>Peyrard <ins style="font-weight: bold; text-decoration: none;">T, </ins>Coghlan <ins style="font-weight: bold; text-decoration: none;">G, </ins>Illum <ins style="font-weight: bold; text-decoration: none;">N, </ins>Birgens <ins style="font-weight: bold; text-decoration: none;">H, </ins>Tamary <ins style="font-weight: bold; text-decoration: none;">H, </ins>Iolascon <ins style="font-weight: bold; text-decoration: none;">A, </ins>Delaunay <ins style="font-weight: bold; text-decoration: none;">J, </ins>Tchernia <ins style="font-weight: bold; text-decoration: none;">G, </ins>Cartron <ins style="font-weight: bold; text-decoration: none;">JP </ins>| title = A <ins style="font-weight: bold; text-decoration: none;">dominant mutation </ins>in the <ins style="font-weight: bold; text-decoration: none;">gene encoding </ins>the <ins style="font-weight: bold; text-decoration: none;">erythroid transcription factor </ins>KLF1 <ins style="font-weight: bold; text-decoration: none;">causes </ins>a <ins style="font-weight: bold; text-decoration: none;">congenital dyserythropoietic anemia </ins>| journal = American Journal of Human Genetics | volume = 87 | issue = 5 | pages = <ins style="font-weight: bold; text-decoration: none;">721–7 | date = November 2010 | pmid = 21055716 </ins>| doi = 10.1016/j.ajhg.2010.10.010 }}</ref> and mice<ref>{{cite journal | <ins style="font-weight: bold; text-decoration: none;">vauthors </ins>= Gillinder KR<ins style="font-weight: bold; text-decoration: none;">, </ins>Ilsley MD<ins style="font-weight: bold; text-decoration: none;">, </ins>Nébor D<ins style="font-weight: bold; text-decoration: none;">, </ins>Sachidanandam R<ins style="font-weight: bold; text-decoration: none;">, </ins>Lajoie M<ins style="font-weight: bold; text-decoration: none;">, </ins>Magor GW<ins style="font-weight: bold; text-decoration: none;">, </ins>Tallack MR<ins style="font-weight: bold; text-decoration: none;">, </ins>Bailey T<ins style="font-weight: bold; text-decoration: none;">, </ins>Landsberg MJ<ins style="font-weight: bold; text-decoration: none;">, </ins>Mackay JP<ins style="font-weight: bold; text-decoration: none;">, </ins>Parker MW<ins style="font-weight: bold; text-decoration: none;">, </ins>Miles LA<ins style="font-weight: bold; text-decoration: none;">, </ins>Graber JH<ins style="font-weight: bold; text-decoration: none;">, </ins>Peters LL<ins style="font-weight: bold; text-decoration: none;">, </ins>Bieker JJ<ins style="font-weight: bold; text-decoration: none;">, </ins>Perkins AC | title = Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability | journal = Nucleic Acids Research <ins style="font-weight: bold; text-decoration: none;">| volume = 45 | issue = 3 | pages = 1130–1143 </ins>| date = <ins style="font-weight: bold; text-decoration: none;">February 2017 | pmid = 28180284 | pmc = 5388391 </ins>| doi = 10.1093/nar/gkw1014 }}</ref> as the cause of a rare inherited anemia [[Congenital dyserythropoietic anemia|CDA type IV]]. <ins style="font-weight: bold; text-decoration: none;">Additional family studies and clinical research<ref>{{cite journal | vauthors = Borg J, Papadopoulos P, Georgitsi M, Gutiérrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgür Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S | title = Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin | journal = Nature Genetics | volume = 42 | issue = 9 | pages = 801–5 | date = September 2010 | pmid = 20676099 | pmc = 2930131 | doi = 10.1038/ng.630 }}</ref> unveiled the molecular genetics of the HPFH KLF1-related condition and established KLF1 as a novel quantitative trait locus for HbF (HBFQTL6).<ref>{{OMIM|613566|HBFQTL6}}</ref> </ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== References==</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>== References==</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>{{Reflist}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>{{Reflist}}</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"></del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">== External links ==</del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">* Cooley's Anemia Foundation. About Thalassemia [Internet]. New York, NY: Cooley's Anemia Foundation National Office; 2001 [1 August 2007] . Available from: http://cooleysanemia.org/sections.php?sec=1&tab=8</del></div></td><td colspan="2" class="diff-side-added"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>{{Transcription factors|g2}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>{{Transcription factors|g2}}</div></td></tr>
</table>
imported>Boghog
https://www.wikidoc.org/index.php?title=KLF1&diff=1418685&oldid=prev
en>JCW-CleanerBot: /* Clinical significance */task, replaced: Nucleic acids research → Nucleic Acids Research using AWB
2017-09-11T11:30:34Z
<p><span dir="auto"><span class="autocomment">Clinical significance: </span><a href="/index.php?title=User:JCW-CleanerBot&action=edit&redlink=1" class="new" title="User:JCW-CleanerBot (page does not exist)">task</a>, replaced: Nucleic acids research → Nucleic Acids Research using <a href="/index.php?title=wikidoc:AWB&action=edit&redlink=1" class="new" title="wikidoc:AWB (page does not exist)">AWB</a></span></p>
<p><b>New page</b></p><div>{{Infobox gene}}<br />
'''Krueppel-like factor 1''' is a [[protein]] that in humans is encoded by the KLF1 [[gene]]. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a [[transcription factor]] that is necessary for the proper maturation of [[erythrocytes|erythroid]] (red blood) cells.<br />
<br />
== Structure ==<br />
The molecule has two domains; the [[Transcription factor#Trans-activating domain|transactivation domain]] and the [[chromatin]]-remodeling domain. The carboxyl (C) terminal is composed of three C2H2 [[zinc finger]]s that binds to DNA, and the amino (N) terminus is proline rich and acidic.<ref name="pmid11739731">{{cite journal |vauthors=Brown RC, Pattison S, van Ree J, Coghill E, Perkins A, Jane SM, Cunningham JM | title = Distinct domains of erythroid Krüppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter | journal = Mol. Cell. Biol. | volume = 22 | issue = 1 | pages = 161–70 |date=January 2002 | pmid = 11739731 | pmc = 134232 | doi = 10.1128/mcb.22.1.161-170.2002}}</ref><br />
<br />
== Function ==<br />
Studies in mice first demonstrated the critical function of KLF1 in hematopoietic development. KLF1 deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult β-globin, and die by embryonic day 15.<ref name="Perkins et al">{{cite journal|last1=Perkins|first1=Andrew|last2=Sharpe|first2=Ariene|last3=Orkin|first3=Stuart|title=Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF.|journal=Nature|date=1995|volume=375|issue=6529|pages=318–322|doi=10.1038/375318a0|pmid=7753195}}</ref><br />
Over-expression of KLF1 results in a reduction of the number of circulating platelets and hastens the onset of the β-globin gene.<ref>{{cite journal|last1=Tewari|first1=Rita|last2=Gillemans|first2=Nynke|last3=Wijgerde|first3=Mark|last4=Nuez|first4=Beatriz|last5=von Lindern|first5=Marieke|last6=Grosveld|first6=Frank|last7=Philipsen|first7=Sjaak|title=Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5 HS3 of the β-globin locus control region|journal=EMBO J|date=1998|volume=17|issue=8|pages=2334–2341|doi=10.1093/emboj/17.8.2334|pmid=9545245}}</ref><br />
<br />
KLF1 coordinates the regulation of six cellular pathways that are all essential to terminal erythroid differentiation:<ref>{{cite journal|last1=Tallack|first1=Michael|last2=Perkins|first2=Andrew|title=KLF1 Directly Coordinates Almost All Aspects of Terminal Erythroid Differentiation|journal=IUBMB Life|date=2010|volume=62|issue=12|pages=886–890|doi=10.1002/iub.404|pmid=21190291}}</ref><br />
<br />
# Cell Membrane & Cytoskeleton<br />
# Apoptosis<br />
# Heme Synthesis & Transport<br />
# Cell Cycling<br />
# Iron Procurement<br />
# Globin Chain Production<br />
<br />
It has also been linked to three main processes that are all essential to transcription of the β globin gene:<br />
# [[Chromatin remodeling]]<br />
# Modulation of the gamma to [[beta globin]] switch<br />
# Transcriptional activation<br />
<br />
KLF1 binds specifically to the "CACCC" motif of the β-globin gene promoter.<ref name="Perkins et al" /> When natural mutations occur in the promoter, β+ [[thalassemia]] can arise in humans. Thalassemia's prevalence (2 million worldwide carry the trait) makes KLF1 clinically significant.<br />
<br />
== Clinical significance ==<br />
Next-Generation sequencing efforts have revealed a surprisingly high prevalence of mutations in human KLF1. The chance of a KLF1 null child being conceived is approximately 1:24,000 in Southern China.<ref name="Perkins review">{{cite journal|last1=Perkins|first1=Andrew|last2=Xu|first2=Xiangmin|last3=Higgs|first3=Douglas|last4=The KLF1 Consensus Workgroup|last5=Patrinos|first5=George|last6=Arnaud|first6=Lionel|last7=Bieker|first7=James|last8=Philipsen|first8=Sjaak|title=Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants.|journal=Blood|date=2016|volume=127|issue=15|pages=1856–1862|doi=10.1182/blood-2016-01-694331|pmid=26903544}}</ref> With pre-natal blood transfusions and bone marrow transplant, it is possible to be born without KLF1.<ref>{{cite journal|last1=Magor|first1=Graham|last2=Tallack|first2=Michael|last3=Gillinder|first3=Kevin|last4=Bell|first4=Charles|last5=McCallum|first5=Naomi|last6=Williams|first6=Bronwyn|last7=Perkins|first7=Andrew|title=KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome|journal=Blood|date=2014|volume=125|issue=15|pages=2405–2417|doi=10.1182/blood-2014-08-590968|pmid=25724378}}</ref> Most mutations in KLF1 lead to a recessive loss-of-function phenotype,<ref name="Perkins review" /> however semi-dominant mutations have been identified in humans<ref>{{cite journal|last1=Arnaud|first1=Lionel|last2=Saison|first2=Carole|last3=Helias|first3=Virginie|last4=Lucien|first4=Nicole|last5=Steschenko|first5=Dominique|last6=Giarratana|first6=Marie-Catherine|last7=Prehu|first7=Claude|last8=Foliguet|first8=Bernard|last9=Montout|first9=Lory|last10=de Brevern|first10=Alexandre G.|last11=Francina|first11=Alain|last12=Ripoche|first12=Pierre|last13=Fenneteau|first13=Odile|last14=Da Costa|first14=Lydie|last15=Peyrard|first15=Thierry|last16=Coghlan|first16=Gail|last17=Illum|first17=Niels|last18=Birgens|first18=Henrik|last19=Tamary|first19=Hannah|last20=Iolascon|first20=Achille|last21=Delaunay|first21=Jean|last22=Tchernia|first22=Gil|last23=Cartron|first23=Jean-Pierre|title=A Dominant Mutation in the Gene Encoding the Erythroid Transcription Factor KLF1 Causes a Congenital Dyserythropoietic Anemia|journal=The American Journal of Human Genetics|date=2010|volume=87|issue=5|pages=721–727|doi=10.1016/j.ajhg.2010.10.010}}</ref> and mice<ref>{{cite journal|last1=Gillinder|first1=KR|last2=Ilsley|first2=MD|last3=Nébor|first3=D|last4=Sachidanandam|first4=R|last5=Lajoie|first5=M|last6=Magor|first6=GW|last7=Tallack|first7=MR|last8=Bailey|first8=T|last9=Landsberg|first9=MJ|last10=Mackay|first10=JP|last11=Parker|first11=MW|last12=Miles|first12=LA|last13=Graber|first13=JH|last14=Peters|first14=LL|last15=Bieker|first15=JJ|last16=Perkins|first16=AC|title=Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability.|journal=Nucleic Acids Research|date=2016|doi=10.1093/nar/gkw1014|pmid=27899603}}</ref> as the cause of a rare inherited anemia [[Congenital dyserythropoietic anemia|CDA type IV]].<br />
<br />
== References==<br />
{{Reflist}}<br />
<br />
== External links ==<br />
* Cooley's Anemia Foundation. About Thalassemia [Internet]. New York, NY: Cooley's Anemia Foundation National Office; 2001 [1 August 2007] . Available from: http://cooleysanemia.org/sections.php?sec=1&tab=8<br />
<br />
{{Transcription factors|g2}}<br />
{{Use dmy dates|date=April 2017}}<br />
<br />
[[Category:Transcription factors]]</div>
en>JCW-CleanerBot