• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Jan 1996; 16(1): 437–441.
PMCID: PMC231020

Quantitative discrimination of MEF2 sites.

Abstract

Myocyte-specific enhancer factor 2 (MEF2) is a family of closely related transcription factors that play a key role in the differentiation of muscle tissues and are important in the muscle-specific expression of a number of genes. Given the centrality of MEF2 in muscle differentiation, regulatory regions newly determined to be muscle specific are often studied for potential MEF2 binding sites. Possible sites are often located by comparison to a homologous gene or by matching to the consensus MEF2 sequence. Enough data have accumulated that a richer description of the MEF2 binding site, a position weight matrix, can be reliably constructed and its usefulness can be assessed. It was shown that scores from such a matrix approximate MEF2 binding energy and enable recognition of naturally occurring MEF2 sites with high sensitivity and specificity. Regulation of genes via MEF2-like sites is complicated by the fact that a number of transcription factors are involved. Not only is MEF2 itself a family of proteins, but several other, nonhomologous, transcription factors overlap MEF2 in DNA-binding specificity. Thus, more quantitative methods for recognizing potential sites may help with the lengthy process of disentangling the complex regulatory circuits of muscle-specific expression.

Full Text

The Full Text of this article is available as a PDF (195K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adolph EA, Subramaniam A, Cserjesi P, Olson EN, Robbins J. Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene. J Biol Chem. 1993 Mar 15;268(8):5349–5352. [PubMed]
  • Andres V, Nadal-Ginard B, Mahdavi V. Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding regulatory proteins differentially expressed during development. Development. 1992 Oct;116(2):321–334. [PubMed]
  • Berg OG, von Hippel PH. Selection of DNA binding sites by regulatory proteins. Trends Biochem Sci. 1988 Jun;13(6):207–211. [PubMed]
  • Black BL, Martin JF, Olson EN. The mouse MRF4 promoter is trans-activated directly and indirectly by muscle-specific transcription factors. J Biol Chem. 1995 Feb 17;270(7):2889–2892. [PubMed]
  • Breitbart RE, Liang CS, Smoot LB, Laheru DA, Mahdavi V, Nadal-Ginard B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993 Aug;118(4):1095–1106. [PubMed]
  • Chambers AE, Kotecha S, Towers N, Mohun TJ. Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis. EMBO J. 1992 Dec;11(13):4981–4991. [PMC free article] [PubMed]
  • Cserjesi P, Lilly B, Bryson L, Wang Y, Sassoon DA, Olson EN. MHox: a mesodermally restricted homeodomain protein that binds an essential site in the muscle creatine kinase enhancer. Development. 1992 Aug;115(4):1087–1101. [PubMed]
  • Cserjesi P, Lilly B, Hinkley C, Perry M, Olson EN. Homeodomain protein MHox and MADS protein myocyte enhancer-binding factor-2 converge on a common element in the muscle creatine kinase enhancer. J Biol Chem. 1994 Jun 17;269(24):16740–16745. [PubMed]
  • Cserjesi P, Olson EN. Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. Mol Cell Biol. 1991 Oct;11(10):4854–4862. [PMC free article] [PubMed]
  • Edmondson DG, Cheng TC, Cserjesi P, Chakraborty T, Olson EN. Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2. Mol Cell Biol. 1992 Sep;12(9):3665–3677. [PMC free article] [PubMed]
  • Fondrat C, Kalogeropoulos A. Approaching the function of new genes by detection of their potential upstream activation sequences in Saccharomyces cerevisiae: application to chromosome III. Curr Genet. 1994 May;25(5):396–406. [PubMed]
  • Gossett LA, Kelvin DJ, Sternberg EA, Olson EN. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol. 1989 Nov;9(11):5022–5033. [PMC free article] [PubMed]
  • Grayson J, Williams RS, Yu YT, Bassel-Duby R. Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter. Mol Cell Biol. 1995 Apr;15(4):1870–1878. [PMC free article] [PubMed]
  • Han TH, Prywes R. Regulatory role of MEF2D in serum induction of the c-jun promoter. Mol Cell Biol. 1995 Jun;15(6):2907–2915. [PMC free article] [PubMed]
  • Hidaka K, Yamamoto I, Arai Y, Mukai T. The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene. Mol Cell Biol. 1993 Oct;13(10):6469–6478. [PMC free article] [PubMed]
  • Horlick RA, Benfield PA. The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements. Mol Cell Biol. 1989 Jun;9(6):2396–2413. [PMC free article] [PubMed]
  • Jurka J, Walichiewicz J, Milosavljevic A. Prototypic sequences for human repetitive DNA. J Mol Evol. 1992 Oct;35(4):286–291. [PubMed]
  • Kaushal S, Schneider JW, Nadal-Ginard B, Mahdavi V. Activation of the myogenic lineage by MEF2A, a factor that induces and cooperates with MyoD. Science. 1994 Nov 18;266(5188):1236–1240. [PubMed]
  • Komuro I, Schalling M, Jahn L, Bodmer R, Jenkins NA, Copeland NG, Izumo S. Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter. EMBO J. 1993 Apr;12(4):1387–1401. [PMC free article] [PubMed]
  • Lawrence CE, Altschul SF, Boguski MS, Liu JS, Neuwald AF, Wootton JC. Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. Science. 1993 Oct 8;262(5131):208–214. [PubMed]
  • Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA. MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1546–1550. [PMC free article] [PubMed]
  • Li H, Capetanaki Y. An E box in the desmin promoter cooperates with the E box and MEF-2 sites of a distal enhancer to direct muscle-specific transcription. EMBO J. 1994 Aug 1;13(15):3580–3589. [PMC free article] [PubMed]
  • Li Z, Paulin D. Different factors interact with myoblast-specific and myotube-specific enhancer regions of the human desmin gene. J Biol Chem. 1993 May 15;268(14):10403–10415. [PubMed]
  • Lilly B, Zhao B, Ranganayakulu G, Paterson BM, Schulz RA, Olson EN. Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science. 1995 Feb 3;267(5198):688–693. [PubMed]
  • Liu ML, Olson AL, Edgington NP, Moye-Rowley WS, Pessin JE. Myocyte enhancer factor 2 (MEF2) binding site is essential for C2C12 myotube-specific expression of the rat GLUT4/muscle-adipose facilitative glucose transporter gene. J Biol Chem. 1994 Nov 11;269(45):28514–28521. [PubMed]
  • Martin JF, Miano JM, Hustad CM, Copeland NG, Jenkins NA, Olson EN. A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing. Mol Cell Biol. 1994 Mar;14(3):1647–1656. [PMC free article] [PubMed]
  • Martin JF, Schwarz JJ, Olson EN. Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5282–5286. [PMC free article] [PubMed]
  • McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B. hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors. Mol Cell Biol. 1993 Apr;13(4):2564–2577. [PMC free article] [PubMed]
  • Molkentin JD, Markham BE. Myocyte-specific enhancer-binding factor (MEF-2) regulates alpha-cardiac myosin heavy chain gene expression in vitro and in vivo. J Biol Chem. 1993 Sep 15;268(26):19512–19520. [PubMed]
  • Molkentin JD, Markham BE. An M-CAT binding factor and an RSRF-related A-rich binding factor positively regulate expression of the alpha-cardiac myosin heavy-chain gene in vivo. Mol Cell Biol. 1994 Aug;14(8):5056–5065. [PMC free article] [PubMed]
  • Naidu PS, Ludolph DC, To RQ, Hinterberger TJ, Konieczny SF. Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. Mol Cell Biol. 1995 May;15(5):2707–2718. [PMC free article] [PubMed]
  • Nakatsuji Y, Hidaka K, Tsujino S, Yamamoto Y, Mukai T, Yanagihara T, Kishimoto T, Sakoda S. A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells. Mol Cell Biol. 1992 Oct;12(10):4384–4390. [PMC free article] [PubMed]
  • Parmacek MS, Ip HS, Jung F, Shen T, Martin JF, Vora AJ, Olson EN, Leiden JM. A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle. Mol Cell Biol. 1994 Mar;14(3):1870–1885. [PMC free article] [PubMed]
  • Pollock R, Treisman R. A sensitive method for the determination of protein-DNA binding specificities. Nucleic Acids Res. 1990 Nov 11;18(21):6197–6204. [PMC free article] [PubMed]
  • Pollock R, Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. [PubMed]
  • Rosenthal N, Berglund EB, Wentworth BM, Donoghue M, Winter B, Bober E, Braun T, Arnold HH. A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors. Nucleic Acids Res. 1990 Nov 11;18(21):6239–6246. [PMC free article] [PubMed]
  • Ruiz-Lozano P, de Lecea L, Buesa C, Pérez de la Osa P, LePage D, Gualberto A, Walsh K, Pons G. The gene encoding rat phosphoglycerate mutase subunit M: cloning and promoter analysis in skeletal muscle cells. Gene. 1994 Sep 30;147(2):243–248. [PubMed]
  • Shore P, Sharrocks AD. The MADS-box family of transcription factors. Eur J Biochem. 1995 Apr 1;229(1):1–13. [PubMed]
  • Stormo GD. Consensus patterns in DNA. Methods Enzymol. 1990;183:211–221. [PubMed]
  • von Hippel PH. Protein-DNA recognition: new perspectives and underlying themes. Science. 1994 Feb 11;263(5148):769–770. [PubMed]
  • Wang G, Yeh HI, Lin JJ. Characterization of cis-regulating elements and trans-activating factors of the rat cardiac troponin T gene. J Biol Chem. 1994 Dec 2;269(48):30595–30603. [PubMed]
  • Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B. Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992 Sep;6(9):1783–1798. [PubMed]
  • Zhu H, Nguyen VT, Brown AB, Pourhosseini A, Garcia AV, van Bilsen M, Chien KR. A novel, tissue-restricted zinc finger protein (HF-1b) binds to the cardiac regulatory element (HF-1b/MEF-2) in the rat myosin light-chain 2 gene. Mol Cell Biol. 1993 Jul;13(7):4432–4444. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...