Myocyte enhancer factor gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

Mef2 was originally identified as a transcription factor complex through promoter analysis of the muscle creatine kinase (mck) gene to identify nuclear factors interacting with the mck enhancer region during muscle differentiation.[1]

Three human mRNA coding sequences designated RSRF (Related to Serum Response Factor) were cloned and shown to dimerize, bind a consensus sequence similar to the one present in the MCK enhancer region, and drive transcription.[2] RSRFs were subsequently demonstrated to encode human genes now named Mef2A, Mef2B and Mef2D.

Myocyte enhancer factor-2 (MEF2) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development.[3] In adult organisms, Mef2 proteins mediate the stress response in some tissues.[3]

Human genes

Vertebrates have at least four versions of the Mef2 gene (human versions are denoted as Myocyte-specific enhancer factor 2A (MEF2A), MEF2B, MEF2C, and MEF2D), all expressed in distinct but overlapping patterns during embryogenesis through adulthood.[4]

Interactions

Consensus sequences

"The current study delineates the conformational paradigm, clustered recognition, and comparative DNA binding preferences for MEF2A and MEF2B-specific MADS-box/MEF2 domains at the YTA(A/T)4TAR consensus motif."[5] Y = (C/T) and R = (A/G). The consensus sequence is (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G).[5]

Myocyte enhancer factor samplings

Main article: Model samplings

Myocyte enhancer factor samplings

Copying an apparent consensus sequence for the TTATAT or CTAATT and putting it in "⌘F" finds two (TTATAT) located between ZSCAN22 and one (CTAATT) between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G) (starting with SuccessablesMYO.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 (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 2, TTATTATTAA at 4226, CTATATATAA at 1601.
  2. positive strand, negative direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 0.
  3. positive strand, positive direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 1, CTAATATTAA at 4169.
  4. negative strand, positive direction, looking for(C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 1, CTAATTTTAA at 2443.

Inverse complement is the same as the direct myocyte enhancer factor.

MEF UTR gene transcriptions

  1. Negative strand, negative direction: TTATTATTAA at 4226.

MEF proximal promoters

  1. Positive strand, positive direction: CTAATATTAA at 4169.

MEF distal promoters

  1. Negative strand, negative direction: CTATATATAA at 1601.
  1. Negative strand, positive direction: CTAATTTTAA at 2443.

Myocyte enhancer factor random dataset samplings

  1. MYOr0: 0.
  2. MYOr1: 0.
  3. MYOr2: 2, CTAAATTTAG at 2521, TTAAATTTAG at 1772.
  4. MYOr3: 0.
  5. MYOr4: 2, TTAATATTAA at 4164, TTATATTTAA at 3724.
  6. MYOr5: 0.
  7. MYOr6: 1, TTAAATATAA at 2239.
  8. MYOr7: 1, CTATAAATAA at 3632.
  9. MYOr8: 0.
  10. MYOr9: 0.
  11. MYOr0ci: 0.
  12. MYOr1ci: 0.
  13. MYOr2ci: 2, CTAAATTTAG at 2521, TTAAATTTAG at 1772.
  14. MYOr3ci: 0.
  15. MYOr4ci: 2, TTAATATTAA at 4164, TTATATTTAA at 3724.
  16. MYOr5ci: 0.
  17. MYOr6ci: 1, TTAAATATAA at 2239.
  18. MYOr7ci: 1, CTATAAATAA at 3632.
  19. MYOr8ci: 0.
  20. MYOr9ci: 0.

MYOr arbitrary (evens) (4560-2846) UTRs

  1. MYOr4: TTAATATTAA at 4164, TTATATTTAA at 3724.

MYOr alternate (odds) (4560-2846) UTRs

  1. MYOr7: CTATAAATAA at 3632.

MYOr alternate positive direction (evens) (4265-4050) proximal promoters

  1. MYOr4: TTAATATTAA at 4164.

MYOr arbitrary negative direction (evens) (2596-1) distal promoters

  1. MYOr2: CTAAATTTAG at 2521, TTAAATTTAG at 1772.
  2. MYOr6: TTAAATATAA at 2239.

MYOr arbitrary positive direction (odds) (4050-1) distal promoters

  1. MYOr7: CTATAAATAA at 3632.

MYOr alternate positive direction (evens) (4050-1) distal promoters

  1. MYOr2: CTAAATTTAG at 2521, TTAAATTTAG at 1772.
  2. MYOr4: TTATATTTAA at 3724.
  3. MYOr6: TTAAATATAA at 2239.

Myocyte enhancer factor analysis and results

Main article: Complex locus A1BG and ZNF497 § Name of response elements

"The current study delineates the conformational paradigm, clustered recognition, and comparative DNA binding preferences for MEF2A and MEF2B-specific MADS-box/MEF2 domains at the YTA(A/T)4TAR consensus motif."[5]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 1 2 0.5 0.5 ± 0.5 (--1,+-0)
Randoms UTR arbitrary negative 2 10 0.2 0.15
Randoms UTR alternate negative 1 10 0.1 0.15
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 0 10 0 0
Randoms Core alternate positive 0 10 0 0
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 0 10 0 0
Randoms Proximal alternate negative 0 10 0 0
Reals Proximal positive 1 2 0.5 0.5 ± 0.5 (-+0,++1)
Randoms Proximal arbitrary positive 0 10 0 0.05
Randoms Proximal alternate positive 1 10 0.1 0.05
Reals Distal negative 1 2 0.5 0.5 ± 0.5 (--1,+-0)
Randoms Distal arbitrary negative 3 10 0.3 0.15
Randoms Distal alternate negative 0 10 0 0.15
Reals Distal positive 1 2 0.5 0.5 ± 0.5 (-+1,++0)
Randoms Distal arbitrary positive 1 10 0.1 0.25
Randoms Distal alternate positive 4 10 0.4 0.25

Comparison:

The occurrences of real myocyte enhancer factors are greater than the randoms. This suggests that the real myocyte enhancer factors are likely active or activable.

See also

References

  1. ↑ Gossett LA, Kelvin DJ, Sternberg EA, Olson EN (1 November 1989). "A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes". Mol. Cell. Biol. 9 (11): 5022–33. doi:10.1128/MCB.9.11.5022. PMC 363654. PMID 2601707.
  2. ↑ Pollock R, Treisman R (1991). "Human SRF-related proteins: DNA-binding properties and potential regulatory targets". Genes Dev. 5 (12a): 2327–41. doi:10.1101/gad.5.12a.2327. PMID 1748287.
  3. ↑ 3.0 3.1 Potthoff MJ, Olson EN (December 2007). "MEF2: a central regulator of diverse developmental programs". Development. 134 (23): 4131–40. doi:10.1242/dev.008367. PMID 17959722. Unknown parameter |s2cid= ignored (help)
  4. ↑ McKinsey TA, Zhang CL, Olson EN (2002). "MEF2: a calcium-dependent regulator of cell division, differentiation and death". Trends Biochem. Sci. 27 (1): 40–7. doi:10.1016/S0968-0004(01)02031-X. PMID 11796223.
  5. ↑ 5.0 5.1 5.2 Ayisha Zia, Muhammad Imran, and Sajid Rashid (7 February 2020). "In Silico Exploration of Conformational Dynamics and Novel Inhibitors for Targeting MEF2-Associated Transcriptional Activity". Journal of Chemical Information and Modeling. 60 (3): 1892–1909. doi:10.1021/acs.jcim.0c00008. Retrieved 10 September 2020.
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