Histone deacetylase
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Histone deacetylases (HDAC) (EC number 3.5.1) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Its action is opposite to that of histone acetyltransferase.
Functions
Deacetylation removes acetyl groups from histone tails, causing the DNA to wrap more tightly around the histones and interfering with the transcription of genes by blocking access by transcription factors. The overall result of histone deacetylation is a global (non specific) reduction in gene expression.
Histone tails are normaly positive charged. The positive charge in them helps them interact very nicely and tighly to the negative charged DNA. Acetyl neutralize the positive charge in the histone; making its interaction with DNA less tight. Thus, dacetylation removes the acetyl groups and restores the positive charge of the histones.
Histone Deacetylase involved in a series of pathway in the living system. In Kyoto Encyclopedia of Genes and Genomes (KEGG), they are:
- Environmental Information Processing; Signal transduction; Notch signaling pathway [PATH:ko04330[1]]
- Cellular Processes; Cell Growth and Death; Cell cycle [PATH:ko04110[2]]
- Human Diseases; Cancers; Chronic myeloid leukemia [PATH:ko05220[3]]
Histone acetylation plays an important role in regulation of gene expression. Hyperacetylated chromatin is transcriptionally active and hypoacetylated is silent. A study on mice found that a specific subset of mouse genes (7%) was deregulated in the absence of HDAC1[1] Their study also found a regulatory cross talk between HDAC1 and HDAC2 and suggest a novel function for HDAC1 as a transcriptional coactivator.
HDAC1 expression was found to be increased in the prefrontal cortex of schizophrenia subjects,[2] negatively correlating with the expression of GAD67 mRNA.
HDAC inhibitors
HDAC inhibitors (HDIs) are being studied as a treatment for cancer and neurodegenerative diseases[3]. The exact mechanisms by which the compounds may work are unclear, but epigenetic pathways are proposed.[4]
HDAC inhibitors may also be associated with the inhibition of some gene promoters. However, this could be due to increased activity of other negative-regulatory proteins.
Family
Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily.[5][6]
Classes of HDACs in higher eukaryotes
HDACs, depending on sequence identity and domain organization, can be organized in three classes:[7]
- Class I
- Class II
- Class III
See also
References
- ↑ Zupkovitz G, Tischler J, Posch M, et al (2006). "Negative and positive regulation of gene expression by mouse histone deacetylase 1". Mol. Cell. Biol. 26 (21): 7913-28. doi:10.1128/MCB.01220-06. PMID 16940178.
- ↑ Sharma RP, Grayson DR, Gavin DP (2007). "Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: Analysis of the National Brain Databank microarray collection". doi:10.1016/j.schres.2007.09.020. PMID 17961987.
- ↑ BBC NEWS. Retrieved on 2007-07-08.
- ↑ Claude Monneret (April 2007). "Histone deacetylase inhibitors for epigenetic therapy of cancer". Anticancer Drugs 18: 363-70.
- ↑ Leipe D.D., Landsman D. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. Nucleic Acids Res. 25: 3693-3697 (1997) PubMed 9278492.
- ↑ InterPro IPR000286 Histone deacetylase superfamily
- ↑ M. Ouaissi and A. Ouaissi. Histone Deacetylase Enzymes as Potential Drug Targets in Cancer and Parasitic Diseases. J Biomed Biotechnol. 2006; 2006: 13474. doi: 10.1155/JBB/2006/13474
External links
Carbon-nitrogen non-peptide hydrolases (EC 3.5) | |
|---|---|
| 3.5.1 - Amidohydrolases | Asparaginase - Glutaminase - Urease - Biotinidase - Aspartoacylase - Ceramidase -Aspartylglucosaminidase - Fatty acid amide hydrolase - Histone deacetylase (Sirtuin) |
| 3.5.2 | Barbiturase - Beta-lactamase |
| 3.5.3 | Arginase |
| 3.5.4 - Aminohydrolases | Guanine deaminase - Adenosine deaminase - AMP deaminase - Inosine monophosphate synthase - DCMP deaminase - GTP cyclohydrolase I |
| Other | Nitrilase - Thiaminase II |
de:Histon-Deacetylase hu:Hiszton deacetiláz
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
