Myocyte enhancer factor gene transcriptions

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]

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:

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.
positive strand, negative direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 0.
positive strand, positive direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 1, CTAATATTAA at 4169.
negative strand, positive direction, looking for(C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 1, CTAATTTTAA at 2443.
complement, negative strand, negative direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 0.
complement, positive strand, negative direction, looking for A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 2, AATAATAATT at 4226, GATATATATT at 1601.
complement, positive strand, positive direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 1, GATTAAAATT at 2443.
complement, negative strand, positive direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 1, GATTATAATT at 4169.
inverse complement, 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.
inverse complement, positive strand, negative direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 0.
inverse complement, positive strand, positive direction, looking for (C/T)TA(A/T)(A/T)(A/T)(A/T)TA(A/G), 1, CTAATATTAA at 4169.
inverse complement, 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 negative strand, negative direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 0.
inverse positive strand, negative direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 2, AATAATAATT at 4226, GATATATATT at 1601.
inverse positive strand, positive direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 1, GATTAAAATT at 2443.
inverse negative strand, positive direction, looking for (A/G)AT(A/T)(A/T)(A/T)(A/T)AT(C/T), 1, GATTATAATT at 4169.

MEF UTR gene transcriptions

Negative strand, negative direction: TTATTATTAA at 4226.

MEF proximal promoters

Positive strand, positive direction: CTAATATTAA at 4169.

MEF distal promoters

Negative strand, negative direction: CTATATATAA at 1601.

Negative strand, positive direction: CTAATTTTAA at 2443.

References

↑ 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.
↑ 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.
↑ ^3.0 ^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)
↑ 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.
↑ ^5.0 ^5.1 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.

External links

[Gossett-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.

[Pollock-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.

[Potthoff-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.

[Zia-5] 5.0 ^5.1 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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