• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 3, 1996; 93(18): 9366–9373.

Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors.


Members of the MyoD family of muscle-specific basic helix-loop-helix (bHLH) proteins function within a genetic pathway to control skeletal muscle development. Mutational analyses of these factors suggested that their DNA binding domains mediated interaction with a coregulator required for activation of muscle-specific transcription. Members of the myocyte enhancer binding factor 2 (MEF2) family of MADS-box proteins are expressed at high levels in muscle and neural cells and at lower levels in several other cell types. MEF2 factors are unable to activate muscle gene expression alone, but they potentiate the transcriptional activity of myogenic bHLH proteins. This potentiation appears to be mediated by direct interactions between the DNA binding domains of these different types of transcription factors. Biochemical and genetic evidence suggests that MEF2 factors are the coregulators for myogenic bHLH proteins. The presence of MEF2 and cell-specific bHLH proteins in other cell types raises the possibility that these proteins may also cooperate to regulate other programs of cell-specific gene expression. We present a model to account for such cooperative interactions.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Buckingham M. Making muscle in mammals. Trends Genet. 1992 Apr;8(4):144–148. [PubMed]
  • Edmondson DG, Olson EN. Helix-loop-helix proteins as regulators of muscle-specific transcription. J Biol Chem. 1993 Jan 15;268(2):755–758. [PubMed]
  • Olson EN, Klein WH. bHLH factors in muscle development: dead lines and commitments, what to leave in and what to leave out. Genes Dev. 1994 Jan;8(1):1–8. [PubMed]
  • Lassar AB, Skapek SX, Novitch B. Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. Curr Opin Cell Biol. 1994 Dec;6(6):788–794. [PubMed]
  • Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD, Lassar AB, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. [PubMed]
  • Olson EN. MyoD family: a paradigm for development? Genes Dev. 1990 Sep;4(9):1454–1461. [PubMed]
  • Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S, et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. [PubMed]
  • Rudnicki MA, Jaenisch R. The MyoD family of transcription factors and skeletal myogenesis. Bioessays. 1995 Mar;17(3):203–209. [PubMed]
  • Muscat GE, Gustafson TA, Kedes L. A common factor regulates skeletal and cardiac alpha-actin gene transcription in muscle. Mol Cell Biol. 1988 Oct;8(10):4120–4133. [PMC free article] [PubMed]
  • Sternberg EA, Spizz G, Perry WM, Vizard D, Weil T, Olson EN. Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene. Mol Cell Biol. 1988 Jul;8(7):2896–2909. [PMC free article] [PubMed]
  • Sartorelli V, Webster KA, Kedes L. Muscle-specific expression of the cardiac alpha-actin gene requires MyoD1, CArG-box binding factor, and Sp1. Genes Dev. 1990 Oct;4(10):1811–1822. [PubMed]
  • French BA, Chow KL, Olson EN, Schwartz RJ. Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter. Mol Cell Biol. 1991 May;11(5):2439–2450. [PMC free article] [PubMed]
  • Wentworth BM, Donoghue M, Engert JC, Berglund EB, Rosenthal N. Paired MyoD-binding sites regulate myosin light chain gene expression. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1242–1246. [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]
  • Bessereau JL, Mendelzon D, LePoupon C, Fiszman M, Changeux JP, Piette J. Muscle-specific expression of the acetylcholine receptor alpha-subunit gene requires both positive and negative interactions between myogenic factors, Sp1 and GBF factors. EMBO J. 1993 Feb;12(2):443–449. [PMC free article] [PubMed]
  • Amacher SL, Buskin JN, Hauschka SD. Multiple regulatory elements contribute differentially to muscle creatine kinase enhancer activity in skeletal and cardiac muscle. Mol Cell Biol. 1993 May;13(5):2753–2764. [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]
  • Wan B, Moreadith RW. Structural characterization and regulatory element analysis of the heart isoform of cytochrome c oxidase VIa. J Biol Chem. 1995 Nov 3;270(44):26433–26440. [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]
  • 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]
  • Walsh K, Schimmel P. Two nuclear factors compete for the skeletal muscle actin promoter. J Biol Chem. 1987 Jul 15;262(20):9429–9432. [PubMed]
  • Thompson WR, Nadal-Ginard B, Mahdavi V. A MyoD1-independent muscle-specific enhancer controls the expression of the beta-myosin heavy chain gene in skeletal and cardiac muscle cells. J Biol Chem. 1991 Nov 25;266(33):22678–22688. [PubMed]
  • Navankasattusas S, Zhu H, Garcia AV, Evans SM, Chien KR. A ubiquitous factor (HF-1a) and a distinct muscle factor (HF-1b/MEF-2) form an E-box-independent pathway for cardiac muscle gene expression. Mol Cell Biol. 1992 Apr;12(4):1469–1479. [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]
  • Weintraub H, Dwarki VJ, Verma I, Davis R, Hollenberg S, Snider L, Lassar A, Tapscott SJ. Muscle-specific transcriptional activation by MyoD. Genes Dev. 1991 Aug;5(8):1377–1386. [PubMed]
  • Schwarz JJ, Chakraborty T, Martin J, Zhou JM, Olson EN. The basic region of myogenin cooperates with two transcription activation domains to induce muscle-specific transcription. Mol Cell Biol. 1992 Jan;12(1):266–275. [PMC free article] [PubMed]
  • Winter B, Braun T, Arnold HH. Co-operativity of functional domains in the muscle-specific transcription factor Myf-5. EMBO J. 1992 May;11(5):1843–1855. [PMC free article] [PubMed]
  • Davis RL, Cheng PF, Lassar AB, Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. [PubMed]
  • Brennan TJ, Chakraborty T, Olson EN. Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5675–5679. [PMC free article] [PubMed]
  • Davis RL, Weintraub H. Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. Science. 1992 May 15;256(5059):1027–1030. [PubMed]
  • Ma PC, Rould MA, Weintraub H, Pabo CO. Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Cell. 1994 May 6;77(3):451–459. [PubMed]
  • Lilly B, Galewsky S, Firulli AB, Schulz RA, Olson EN. D-MEF2: a MADS box transcription factor expressed in differentiating mesoderm and muscle cell lineages during Drosophila embryogenesis. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5662–5666. [PMC free article] [PubMed]
  • Nguyen HT, Bodmer R, Abmayr SM, McDermott JC, Spoerel NA. D-mef2: a Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7520–7524. [PMC free article] [PubMed]
  • Taylor MV, Beatty KE, Hunter HK, Baylies MK. Drosophila MEF2 is regulated by twist and is expressed in both the primordia and differentiated cells of the embryonic somatic, visceral and heart musculature. Mech Dev. 1995 Mar;50(1):29–41. [PubMed]
  • Venuti JM, Gan L, Kozlowski MT, Klein WH. Developmental potential of muscle cell progenitors and the myogenic factor SUM-1 in the sea urchin embryo. Mech Dev. 1993 Apr;41(1):3–14. [PubMed]
  • Braun T, Arnold HH. The four human muscle regulatory helix-loop-helix proteins Myf3-Myf6 exhibit similar hetero-dimerization and DNA binding properties. Nucleic Acids Res. 1991 Oct 25;19(20):5645–5651. [PMC free article] [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]
  • Olson EN, Perry M, Schulz RA. Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol. 1995 Nov;172(1):2–14. [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]
  • Pollock R, Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. [PubMed]
  • Dodou E, Sparrow DB, Mohun T, Treisman R. MEF2 proteins, including MEF2A, are expressed in both muscle and non-muscle cells. Nucleic Acids Res. 1995 Nov 11;23(21):4267–4274. [PMC free article] [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]
  • 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]
  • 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]
  • 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]
  • Chambers AE, Logan M, Kotecha S, Towers N, Sparrow D, Mohun TJ. The RSRF/MEF2 protein SL1 regulates cardiac muscle-specific transcription of a myosin light-chain gene in Xenopus embryos. Genes Dev. 1994 Jun 1;8(11):1324–1334. [PubMed]
  • Wong MW, Pisegna M, Lu MF, Leibham D, Perry M. Activation of Xenopus MyoD transcription by members of the MEF2 protein family. Dev Biol. 1994 Dec;166(2):683–695. [PubMed]
  • Shore P, Sharrocks AD. The MADS-box family of transcription factors. Eur J Biochem. 1995 Apr 1;229(1):1–13. [PubMed]
  • Molkentin JD, Firulli AB, Black BL, Martin JF, Hustad CM, Copeland N, Jenkins N, Lyons G, Olson EN. MEF2B is a potent transactivator expressed in early myogenic lineages. Mol Cell Biol. 1996 Jul;16(7):3814–3824. [PMC free article] [PubMed]
  • Braun T, Tannich E, Buschhausen-Denker G, Arnold HH. Promoter upstream elements of the chicken cardiac myosin light-chain 2-A gene interact with trans-acting regulatory factors for muscle-specific transcription. Mol Cell Biol. 1989 Jun;9(6):2513–2525. [PMC free article] [PubMed]
  • Iannello RC, Mar JH, Ordahl CP. Characterization of a promoter element required for transcription in myocardial cells. J Biol Chem. 1991 Feb 15;266(5):3309–3316. [PubMed]
  • Zhu H, Garcia AV, Ross RS, Evans SM, Chien KR. A conserved 28-base-pair element (HF-1) in the rat cardiac myosin light-chain-2 gene confers cardiac-specific and alpha-adrenergic-inducible expression in cultured neonatal rat myocardial cells. Mol Cell Biol. 1991 Apr;11(4):2273–2281. [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]
  • Muscat GE, Perry S, Prentice H, Kedes L. The human skeletal alpha-actin gene is regulated by a muscle-specific enhancer that binds three nuclear factors. Gene Expr. 1992;2(2):111–126. [PubMed]
  • Morisaki T, Holmes EW. Functionally distinct elements are required for expression of the AMPD1 gene in myocytes. Mol Cell Biol. 1993 Sep;13(9):5854–5860. [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]
  • 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]
  • 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]
  • 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]
  • Suzuki E, Guo K, Kolman M, Yu YT, Walsh K. Serum induction of MEF2/RSRF expression in vascular myocytes is mediated at the level of translation. Mol Cell Biol. 1995 Jun;15(6):3415–3423. [PMC free article] [PubMed]
  • Molkentin JD, Black BL, Martin JF, Olson EN. Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C. Mol Cell Biol. 1996 Jun;16(6):2627–2636. [PMC free article] [PubMed]
  • Sharrocks AD, von Hesler F, Shaw PE. The identification of elements determining the different DNA binding specificities of the MADS box proteins p67SRF and RSRFC4. Nucleic Acids Res. 1993 Jan 25;21(2):215–221. [PMC free article] [PubMed]
  • Nurrish SJ, Treisman R. DNA binding specificity determinants in MADS-box transcription factors. Mol Cell Biol. 1995 Aug;15(8):4076–4085. [PMC free article] [PubMed]
  • Pellegrini L, Tan S, Richmond TJ. Structure of serum response factor core bound to DNA. Nature. 1995 Aug 10;376(6540):490–498. [PubMed]
  • Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev. 1994 Feb;4(1):96–101. [PubMed]
  • Edmondson DG, Lyons GE, Martin JF, Olson EN. Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis. Development. 1994 May;120(5):1251–1263. [PubMed]
  • Firulli AB, Miano JM, Bi W, Johnson AD, Casscells W, Olson EN, Schwarz JJ. Myocyte enhancer binding factor-2 expression and activity in vascular smooth muscle cells. Association with the activated phenotype. Circ Res. 1996 Feb;78(2):196–204. [PubMed]
  • Lyons GE, Micales BK, Schwarz J, Martin JF, Olson EN. Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation. J Neurosci. 1995 Aug;15(8):5727–5738. [PubMed]
  • Lassar AB, Davis RL, Wright WE, Kadesch T, Murre C, Voronova A, Baltimore D, Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. [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]
  • Buchberger A, Ragge K, Arnold HH. The myogenin gene is activated during myocyte differentiation by pre-existing, not newly synthesized transcription factor MEF-2. J Biol Chem. 1994 Jun 24;269(25):17289–17296. [PubMed]
  • Cheng TC, Wallace MC, Merlie JP, Olson EN. Separable regulatory elements governing myogenin transcription in mouse embryogenesis. Science. 1993 Jul 9;261(5118):215–218. [PubMed]
  • Yee SP, Rigby PW. The regulation of myogenin gene expression during the embryonic development of the mouse. Genes Dev. 1993 Jul;7(7A):1277–1289. [PubMed]
  • Leibham D, Wong MW, Cheng TC, Schroeder S, Weil PA, Olson EN, Perry M. Binding of TFIID and MEF2 to the TATA element activates transcription of the Xenopus MyoDa promoter. Mol Cell Biol. 1994 Jan;14(1):686–699. [PMC free article] [PubMed]
  • Pinney DF, de la Brousse FC, Faerman A, Shani M, Maruyama K, Emerson CP., Jr Quail myoD is regulated by a complex array of cis-acting control sequences. Dev Biol. 1995 Jul;170(1):21–38. [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]
  • Funk WD, Wright WE. Cyclic amplification and selection of targets for multicomponent complexes: myogenin interacts with factors recognizing binding sites for basic helix-loop-helix, nuclear factor 1, myocyte-specific enhancer-binding factor 2, and COMP1 factor. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9484–9488. [PMC free article] [PubMed]
  • Molkentin JD, Black BL, Martin JF, Olson EN. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell. 1995 Dec 29;83(7):1125–1136. [PubMed]
  • Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN, Klein WH. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature. 1993 Aug 5;364(6437):501–506. [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]
  • Wefald FC, Devlin BH, Williams RS. Functional heterogeneity of mammalian TATA-box sequences revealed by interaction with a cell-specific enhancer. Nature. 1990 Mar 15;344(6263):260–262. [PubMed]
  • Takeda S, North DL, Diagana T, Miyagoe Y, Lakich MM, Whalen RG. Myogenic regulatory factors can activate TATA-containing promoter elements via an E-box independent mechanism. J Biol Chem. 1995 Jun 30;270(26):15664–15670. [PubMed]
  • Schulz RA, Chromey C, Lu MF, Zhao B, Olson EN. Expression of the D-MEF2 transcription in the Drosophila brain suggests a role in neuronal cell differentiation. Oncogene. 1996 Apr 18;12(8):1827–1831. [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]
  • Bour BA, O'Brien MA, Lockwood WL, Goldstein ES, Bodmer R, Taghert PH, Abmayr SM, Nguyen HT. Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev. 1995 Mar 15;9(6):730–741. [PubMed]
  • Olson EN, Perry M, Schulz RA. Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol. 1995 Nov;172(1):2–14. [PubMed]
  • Martin JF, Li L, Olson EN. Repression of myogenin function by TGF-beta 1 is targeted at the basic helix-loop-helix motif and is independent of E2A products. J Biol Chem. 1992 Jun 5;267(16):10956–10960. [PubMed]
  • Kopan R, Nye JS, Weintraub H. The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development. 1994 Sep;120(9):2385–2396. [PubMed]
  • Li L, Chambard JC, Karin M, Olson EN. Fos and Jun repress transcriptional activation by myogenin and MyoD: the amino terminus of Jun can mediate repression. Genes Dev. 1992 Apr;6(4):676–689. [PubMed]
  • Tapscott SJ, Thayer MJ, Weintraub H. Deficiency in rhabdomyosarcomas of a factor required for MyoD activity and myogenesis. Science. 1993 Mar 5;259(5100):1450–1453. [PubMed]
  • Li L, Zhou J, James G, Heller-Harrison R, Czech MP, Olson EN. FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. Cell. 1992 Dec 24;71(7):1181–1194. [PubMed]
  • Lee KJ, Ross RS, Rockman HA, Harris AN, O'Brien TX, van Bilsen M, Shubeita HE, Kandolf R, Brem G, Price J, et al. Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory programs for cardiac and skeletal muscle-specific expression of a single contractile protein gene. J Biol Chem. 1992 Aug 5;267(22):15875–15885. [PubMed]
  • Lee KJ, Hickey R, Zhu H, Chien KR. Positive regulatory elements (HF-1a and HF-1b) and a novel negative regulatory element (HF-3) mediate ventricular muscle-specific expression of myosin light-chain 2-luciferase fusion genes in transgenic mice. Mol Cell Biol. 1994 Feb;14(2):1220–1229. [PMC free article] [PubMed]
  • Navankasattusas S, Sawadogo M, van Bilsen M, Dang CV, Chien KR. The basic helix-loop-helix protein upstream stimulating factor regulates the cardiac ventricular myosin light-chain 2 gene via independent cis regulatory elements. Mol Cell Biol. 1994 Nov;14(11):7331–7339. [PMC free article] [PubMed]
  • Zou Y, Chien KR. EFIA/YB-1 is a component of cardiac HF-1A binding activity and positively regulates transcription of the myosin light-chain 2v gene. Mol Cell Biol. 1995 Jun;15(6):2972–2982. [PMC free article] [PubMed]
  • Molkentin JD, Jobe SM, Markham BE. Alpha-myosin heavy chain gene regulation: delineation and characterization of the cardiac muscle-specific enhancer and muscle-specific promoter. J Mol Cell Cardiol. 1996 Jun;28(6):1211–1225. [PubMed]
  • Srivastava D, Cserjesi P, Olson EN. A subclass of bHLH proteins required for cardiac morphogenesis. Science. 1995 Dec 22;270(5244):1995–1999. [PubMed]
  • Cross JC, Flannery ML, Blanar MA, Steingrimsson E, Jenkins NA, Copeland NG, Rutter WJ, Werb Z. Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development. 1995 Aug;121(8):2513–2523. [PubMed]
  • Hollenberg SM, Sternglanz R, Cheng PF, Weintraub H. Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system. Mol Cell Biol. 1995 Jul;15(7):3813–3822. [PMC free article] [PubMed]
  • Jan YN, Jan LY. HLH proteins, fly neurogenesis, and vertebrate myogenesis. Cell. 1993 Dec 3;75(5):827–830. [PubMed]
  • Lee JE, Hollenberg SM, Snider L, Turner DL, Lipnick N, Weintraub H. Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science. 1995 May 12;268(5212):836–844. [PubMed]
  • Grueneberg DA, Natesan S, Alexandre C, Gilman MZ. Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science. 1992 Aug 21;257(5073):1089–1095. [PubMed]
  • Herskowitz I. A regulatory hierarchy for cell specialization in yeast. Nature. 1989 Dec 14;342(6251):749–757. [PubMed]
  • Dolan JW, Fields S. Cell-type-specific transcription in yeast. Biochim Biophys Acta. 1991 Feb 16;1088(2):155–169. [PubMed]
  • Hu JS, Olson EN, Kingston RE. HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors. Mol Cell Biol. 1992 Mar;12(3):1031–1042. [PMC free article] [PubMed]
  • Michelson AM, Abmayr SM, Bate M, Arias AM, Maniatis T. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 1990 Dec;4(12A):2086–2097. [PubMed]
  • Paterson BM, Walldorf U, Eldridge J, Dübendorfer A, Frasch M, Gehring WJ. The Drosophila homologue of vertebrate myogenic-determination genes encodes a transiently expressed nuclear protein marking primary myogenic cells. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3782–3786. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...