Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family.
Establishment of skeletal muscle and neural cell types is controlled by families of myogenic and neurogenic basic helix-loop-helix (bHLH) proteins, respectively. Myogenic bHLH proteins have been shown to activate skeletal muscle transcription in collaboration with members of the myocyte enhancer factor-2 (MEF2) family of MCM1-agamous-deficiens-serum response factor (MADS)-box transcription factors, which are expressed in differentiated myocytes and neurons. Here, we show that the neurogenic bHLH protein MASH1 interacts with members of the MEF2 family and that this interaction, mediated by the DNA binding and dimerization domains of these factors, results in synergistic activation of transcription through either the MASH1 or the MEF2 DNA binding site. Consistent with their involvement in activation of neuronal gene expression, members of the MEF2 family are expressed in P19 embryonal carcinoma cells that have been induced to form neurons following treatment with retinoic acid. These results suggest that members of the MEF2 family perform similar roles in synergistic activation of transcription in myogenic and neurogenic lineages by serving as cofactors for cell type-specific bHLH proteins.
Black
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BL
Department of Molecular Biology and Oncology, Hamon Center for Basic Cancer Research, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Ligon
K L
KL
Zhang
Y
Y
Olson
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EN
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D064326:MEF2 Transcription Factors; D051379:Mice; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; C499317:Ascl1 protein, mouse