M box gene transcriptions

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Editor-In-Chief: Henry A. Hoff

File:RhodeusSericeusBitterlingMaleSpawingColors.JPG
The dark appearance of the dorsal side of the male bitterling Rhodeus amarus is caused by a dispersal of melanosomes in simulate the dark bottom of the fish tank. Credit: Viridiflavus.

"In melanocytes and in melanoma cells, cyclic AMP (cAMP)-elevating agents stimulate melanogenesis and increase the transcription of tyrosinase, the rate-limiting enzyme in melanin synthesis. However, two other enzymes, tyrosinase-related protein 1 (TRP1) and TRP2, are required for a normal melanization process leading to eumelanin synthesis. In B16 melanoma cells, we demonstrated that stimulation of melanogenesis by cAMP-elevating agents results in an increase in tyrosinase, TRP1, and TRP2 expression. cAMP, through a cAMP-dependent protein kinase pathway, stimulates TRP1 and TRP2 promoter activities in both B16 mouse melanoma cells and normal human melanocytes. Regulation of the TRP1 and TRP2 promoters by cAMP involves a M box and an E box."[1]

"[M]icrophthalmia, a basic helix-loop-helix transcription factor, strongly stimulates the transcriptional activities of the TRP1 and TRP2 promoters, mainly through binding to the M boxes."[1]

"In mammals, pigmentation results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. Melanin synthesis (melanogenesis) takes place in the melanocyte after differentiation of the nonpigmented precursor, the melanoblast (27). Three melanocyte-specific enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1), and TRP2, are involved in this enzymatic process that converts tyrosine to melanin pigments. Although these proteins have similar structures and features, they are expressed by different genes and possess distinct enzymatic activities. Tyrosinase, encoded by the albino locus of the mouse, catalyzes the conversion of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and of DOPA to DOPA quinone (14, 25, 31). TRP2, encoded by the mouse slaty locus, possesses a Dopachrome tautomerase activity, converting the Dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) (3, 19, 42). TRP1, which has been mapped in mouse to the brown locus, catalyzes the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid (21, 24)."[1]

"In the TRP1 promoter, the M box (GTCATGTGCT) [is] located between bp −44 and −33 upstream from the initiation start site [...] and the E box (CAAGTG) [is] located between bp −238 and −233 [...] In the TRP2 promoter, the M box (GTCATGTGCT) [is] located between bp −135 and −129 upstream from the initiation start site [...] the E box (CACATG) [is] between bp −346 and −340 [and] the cAMP response element (CRE; TGAGGTCA) [is] located between bp −239 and −232 [...]."[1]

The "regulation of TRP1 gene expression by PKA in B16 melanoma cells involves the M box just upstream of the TATA box."[1]

Human genes

Gene ID: 1638 is DCT dopachrome tautomerase, aka TRP-2; TYRP2.[2]

  1. NP_001123361.1 L-dopachrome tautomerase isoform 2 precursor: "Transcript Variant: This variant (2) includes two alternate in-frame exons and is predicted to encode a slightly longer protein isoform (2) compared to isoform 1."[2]
  2. NP_001309111.1 L-dopachrome tautomerase isoform 3.[2]
  3. NP_001309112.1 L-dopachrome tautomerase isoform 3.[2]
  4. NP_001309113.1 L-dopachrome tautomerase isoform 3.[2]
  5. NP_001309114.1 L-dopachrome tautomerase isoform 3.[2]
  6. NP_001309115.1 L-dopachrome tautomerase isoform 4.[2]
  7. NP_001913.2 L-dopachrome tautomerase isoform 1 precursor: "Transcript Variant: This variant (1) represents the more abundant transcript."[2]

Gene ID: 7306 is TYRP1 tyrosinase related protein 1: "This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III."[3]

Consensus sequences

"Tyrosinase and TRP1 promoters share an 11-bp motif (AGTCATGTGCT) termed the M box located upstream of the TATA box. This motif binds microphthalmia, a basic helix-loop-helix transcription factor that increases tyrosinase and TRP1 promoter activities, thereby playing a key role in the tissue-specific expression of these genes (11, 29, 40). In the TRP2 promoter, a homologous sequence (GTCATGTGCT) is also found upstream of the TATA box (41)."[1]

"The conserved region contains a consensus M-box element (TCACATGA) for binding of MITF. This MITF binding site is aligned and conserved between at least 11 different species [...]. The clear conservation of these elements suggests that gpnmb has similar regulation in all mammals."[4]

M box (Bertolotto) samplings

Copying a responsive elements consensus sequence GTCATGTGCT and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence GTCATGTGCT (starting with SuccessablesMbox.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for GTCATGTGCT, 0.
  2. positive strand, negative direction, looking for GTCATGTGCT, 0.
  3. positive strand, positive direction, looking for GTCATGTGCT, 0.
  4. negative strand, positive direction, looking for GTCATGTGCT, 0.
  5. inverse complement, negative strand, negative direction, looking for AGCACATGAC, 0.
  6. inverse complement, positive strand, negative direction, looking for AGCACATGAC, 0.
  7. inverse complement, positive strand, positive direction, looking for AGCACATGAC, 0.
  8. inverse complement, negative strand, positive direction, looking for AGCACATGAC, 0.

M-box (Hoek) samplings

Copying a responsive elements consensus sequence (T/N)(C/T)(A/G)TG(A/N) and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (T/N)(C/T)(A/G)TG(A/N) (starting with SuccessablesMHbox.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for (T/N)(C/T)(A/G)TG(A/N), 67, CTGTGC at 4470, ACGTGA at 4340, TTGTGA at 4335, TTGTGT at 4196, TTGTGA at 3982, GTGTGG at 3967, TCGTGT at 3915, GTATGG at 3858, TCGTGA at 3734, TTGTGT at 3670, CCGTGT at 3632, CTATGC at 3546, TTATGA at 3540, TTGTGT at 3513, CTGTGT at 3391, ACGTGA at 3289, CCGTGC at 3230, TCGTGA at 3073, GTATGG at 2993, TCGTGA at 2918, ACGTGG at 2761, ATGTGT at 2687, CCGTGT at 2665, ATATGT at 2641, TTGTGA at 2550, CCGTGC at 2523, ACGTGA at 2426, GTGTGG at 2418, TCATGG at 2343, TTATGT at 2304, TCATGA at 2214, CTATGT at 2179, TTATGA at 2161, TCGTGA at 2097, ACGTGA at 2000, TTATGT at 1877, TCGTGA at 1788, ACGTGT at 1719, CTATGG at 1667, TTATGT at 1565, GTGTGA at 1543, TTGTGT at 1541, ACGTGA at 1347, ACGTGG at 1339, TCGTGA at 1143, GTGTGG at 1128, CCGTGT at 1116, GTGTGC at 962, CCGTGT at 960, GTGTGG at 882, ACATGG at 798, TTATGT at 768, CTGTGG at 748, TCGTGA at 679, CCGTGC at 652, TTATGT at 634, TCGTGA at 543, GTGTGC at 530, CCGTGT at 518, TTATGC at 491, TCGTGA at 406, TTGTGC at 341, ACATGA at 325, CCGTGT at 266, ATATGT at 112, ATGTGG at 61, CTATGT at 59.
  2. positive strand, negative direction, looking for (T/N)(C/T)(A/G)TG(A/N), 51, CTGTGC at 4401, GTGTGA at 4361, GCATGC at 4248, ACGTGG at 4238, TCATGC at 4117, GCATGG at 4107, ATGTGA at 4092, CTGTGG at 3959, GTATGT at 3831, ATGTGG at 3810, CTGTGG at 3711, GTGTGC at 3560, CTGTGT at 3558, CTGTGC at 3428, CTGTGA at 3267, GTGTGG at 3186, GCGTGG at 3047, ATATGT at 2984, GTGTGC at 2862, GCATGA at 2784, TCATGC at 2752, ACATGC at 2668, GTGTGG at 2658, ACATGG at 2614, GTGTGG at 2605, TCATGC at 2534, GCATGC at 2323, GCATGG at 2277, ACATGG at 2152, ATGTGG at 2065, GCATGA at 1953, GCGTGG at 1897, ACATGT at 1850, ATATGG at 1742, GTGTGA at 1479, GCGTGG at 1244, CCGTGT at 1220, ACATGG at 1207, GCATGG at 953, GTGTGT at 795, ATGTGG at 787, GCGTGG at 741, GTGTGT at 610, ATATGG at 605, TTATGA at 351, ATATGA at 274, CTATGT at 212, TCATGG at 201, GCATGA at 124, ATATGG at 77, ATATGT at 42.
  3. positive strand, positive direction, looking for (T/N)(C/T)(A/G)TG(A/N), 76, ACGTGG at 4343, CTGTGA at 4334, TTGTGC at 4258, GTATGT at 4151, CCGTGA at 4006, ACGTGG at 3885, GTGTGG at 3824, TCGTGT at 3740, TCGTGG at 3601, CTGTGG at 3532, GTGTGA at 3507, GTGTGT at 3411, CCGTGT at 3409, ACGTGA at 3343, ACGTGG at 3322, CCATGA at 3115, GTGTGT at 3098, TTGTGT at 3096, TCGTGG at 3044, GTGTGG at 2964, ACGTGT at 2962, TTGTGT at 2835, CTATGA at 2739, GTGTGA at 2636, GTGTGG at 2602, TCATGG at 2597, ATATGG at 2590, GCGTGG at 2566, ATGTGG at 2430, TCGTGA at 2201, TCGTGA at 2105, CCGTGA at 1996, ACGTGT at 1822, GTGTGC at 1697, CTGTGT at 1695, CCGTGC at 1640, TCGTGG at 1628, GTGTGC at 1558, GCGTGT at 1556, GCGTGC at 1552, ACGTGA at 1472, TCGTGG at 1460, ACGTGA at 1372, TCGTGG at 1360, GCGTGC at 1300, GTGTGC at 1222, ACGTGT at 1220, TCGTGG at 1208, GTGTGA at 1138, GCGTGT at 1136, GCGTGC at 1132, TCGTGG at 1124, GCGTGT at 1052, GCGTGC at 1048, TCGTGG at 1040, GTGTGC at 986, GCGTGC at 978, TCGTGG at 956, GTGTGC at 886, GCGTGC at 878, TCGTGG at 856, GTGTGC at 802, GCGTGT at 800, GCGTGC at 796, TCGTGG at 788, TCGTGG at 772, GTGTGT at 716, CTGTGT at 714, GCGTGA at 686, TCGTGG at 620, ATGTGC at 568, GCATGT at 566, GTGTGT at 550, ACGTGT at 548, GTGTGA at 345, CCATGA at 127.
  4. negative strand, positive direction, looking for (T/N)(C/T)(A/G)TG(A/N), 56, CTGTGG at 4394, TCGTGG at 4377, CCATGC at 4371, TCATGT at 4365, CCATGG at 4222, ACATGA at 4154, GTGTGA at 3971, GTGTGG at 3966, ATGTGC at 3959, ACATGT at 3957, ATGTGA at 3903, CCATGT at 3901, CCATGC at 3828, CCGTGG at 3813, ACATGT at 3743, ACATGA at 3708, CTGTGG at 3642, GTGTGA at 3594, CCATGG at 3581, CTGTGG at 3436, CCATGT at 3336, CTATGA at 3260, ATATGG at 3162, GCATGC at 3141, TTATGA at 3027, CTGTGC at 2959, TTGTGC at 2680, GCGTGA at 2555, CCATGT at 2474, TCATGG at 2267, CTGTGT at 2252, CTATGG at 2159, GCATGC at 2154, ACATGA at 2141, CTGTGT at 2076, ACATGG at 2032, GTGTGG at 1971, CCATGC at 1934, ACATGT at 1872, GTGTGG at 1805, GCGTGA at 1720, TCGTGC at 1520, GCGTGC at 1243, TCATGC at 1239, GCGTGC at 1217, TCATGG at 1187, GTGTGG at 1022, GCGTGT at 1020, TCGTGC at 1016, CTGTGG at 918, CTGTGG at 818, ACGTGC at 571, GCGTGC at 545, CTGTGT at 266, ATGTGA at 230, TCGTGT at 80.
  5. inverse complement, negative strand, negative direction, looking for (N/T)CA(C/T)(A/G)(N/A), 0.
  6. inverse complement, positive strand, negative direction, looking for TTTTTTTT, 0.
  7. inverse complement, positive strand, positive direction, looking for TTTTTTTT, 0.
  8. inverse complement, negative strand, positive direction, looking for TTTTTTTT, 0.

MHbox UTRs

MHbox core promoters

MHbox proximal promoters

MHbox distal promoters

MHbox random dataset samplings

  1. MHboxr0: 0.
  2. MHboxr1: 0.
  3. MHboxr2: 0.
  4. MHboxr3: 0.
  5. MHboxr4: 0.
  6. MHboxr5: 0.
  7. MHboxr6: 0.
  8. MHboxr7: 0.
  9. MHboxr8: 0.
  10. MHboxr9: 0.
  11. MHboxr0ci: 0.
  12. MHboxr1ci: 0.
  13. MHboxr2ci: 0.
  14. MHboxr3ci: 0.
  15. MHboxr4ci: 0.
  16. MHboxr5ci: 0.
  17. MHboxr6ci: 0.
  18. MHboxr7ci: 0.
  19. MHboxr8ci: 0.
  20. MHboxr9ci: 0.

MHboxr UTRs

MHboxr core promoters

MHboxr proximal promoters

MHboxr distal promoters

M-box (Ripoll) samplings

Copying a responsive elements consensus sequence TCACATGA and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence TCACATGA (starting with SuccessablesM-box.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for TCACATGA, 1, TCACATGA at 325.
  2. positive strand, negative direction, looking for TCACATGA, 0.
  3. positive strand, positive direction, looking for TCACATGA, 0.
  4. negative strand, positive direction, looking for TCACATGA, 0.
  5. complement, negative strand, negative direction, looking for AGTGTACT, 0.
  6. complement, positive strand, negative direction, looking for AGTGTACT, 1, AGTGTACT at 325.
  7. complement, positive strand, positive direction, looking for AGTGTACT, 0.
  8. complement, negative strand, positive direction, looking for AGTGTACT, 0.
  9. inverse complement, negative strand, negative direction, looking for TCATGTGA, 0.
  10. inverse complement, positive strand, negative direction, looking for TCATGTGA, 0.
  11. inverse complement, positive strand, positive direction, looking for TCATGTGA, 0.
  12. inverse complement, negative strand, positive direction, looking for TCATGTGA, 0.
  13. inverse negative strand, negative direction, looking for AGTACACT, 0.
  14. inverse positive strand, negative direction, looking for AGTACACT, 0.
  15. inverse positive strand, positive direction, looking for AGTACACT, 0.
  16. inverse negative strand, positive direction, looking for AGTACACT, 0.

M-box distal promoters

Negative strand, negative direction: TCACATGA at 325.

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikiversity.

See also

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 Corine Bertolotto, Roser Buscà, Patricia Abbe, Karine Bille, Edith Aberdam, Jean-Paul Ortonne, and Robert Ballotti (February 1998). "Different cis-Acting Elements Are Involved in the Regulation of TRP1 and TRP2 Promoter Activities by Cyclic AMP: Pivotal Role of M Boxes (GTCATGTGCT) and of Microphthalmia". Molecular and Cellular Biology. 18 (2): 694–702. PMID 9447965. Retrieved 8 December 2018.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 HGNC (21 December 2019). "DCT dopachrome tautomerase [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 29 January 2020.
  3. RefSeq (March 2009). "TYRP1 tyrosinase related protein 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 29 January 2020.
  4. Vera M. Ripoll, Nicholas A. Meadows, Liza-Jane Raggatt, Ming K. Chang, Allison R. Pettit, Alan I. Cassady and David A. Hume (30 April 2005). "Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB" (PDF). Gene. 413 (1–2): 32–41. doi:10.1016/j.gene.2008.01.014. Retrieved 18 March 2021.

External links