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

Main article: 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

Main article: Consensus sequence gene transcriptions

"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

Main article: Model 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

Main article: Model samplings

Copying a responsive elements consensus sequence (T/N)CA(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)CA(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)CA(C/T)(A/G)TG(A/N), 2, ACACATGG at 798, TCACATGA at 325.
  2. positive strand, negative direction, looking for (T/N)CA(C/T)(A/G)TG(A/N), 2, GCACATGC at 2668, CCATATGT at 42.
  3. positive strand, positive direction, looking for (T/N)CA(C/T)(A/G)TG(A/N), 5, CCACGTGG at 3885, ACACGTGT at 2962, GCACGTGT at 1220, GCATGTGC at 568, GCACGTGT at 548.
  4. negative strand, positive direction, looking for (T/N)CA(C/T)(A/G)TG(A/N), 7, ACATGTGC at 3959, TCACATGT at 3957, CCATGTGA at 3903, GCACATGT at 3743, CCACATGA at 3708, CCACATGG at 2032, ACACGTGC at 571.

Inverse complement is the same as the first four.

MHbox distal promoters

Main article: Distal promoter gene transcriptions
  1. Negative strand, negative direction: TCACATGA at 325.
  1. Negative strand, positive direction: TCACATGT at 3957, CCATGTGA at 3903, CCACATGA at 3708.

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

Main article: UTR promoter gene transcriptions

MHboxr core promoters

Main article: Core promoter gene transcriptions

MHboxr proximal promoters

Main article: Proximal promoter gene transcriptions

MHboxr distal promoters

Main article: Distal promoter gene transcriptions

M-box (Ripoll) samplings

Main article: Model 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

Main article: Distal promoter gene transcriptions

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

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