MyoD and MEF2A mediate activation and repression of the p75NGFR gene during muscle development.
In an effort to clarify transient expression of the NGF low-affinity receptor p75NGFR during muscle development we have focused on the molecular mechanisms involved in the initiation and cessation of p75NGFR gene expression. Using quiescent C3H10T1/2 fibroblast as a tool, we observed that induction of differentiation competence in MyoD-transfected 10T1/2 fibroblasts was accompanied by the initiation of p75NGFR expression. Moreover, we could show that the bHLH transcription factor MyoD itself is a powerful candidate for transcriptional activation of the p75NGFR gene in muscle precursor cells. By means of MyoD-mutants we have found that both the amino terminus of the MyoD molecule as well as the bHLH-region are essential for transcriptional activity on the p75NGFR promoter. The fact that myocyte enhancer factor MEF2A inactivated MyoD-induced p75NGFR promoter activity strongly suggests that cell-specific regulation of the p75NGFR gene might be strictly dependent on the intracellular composition and balance of the appropriate bHLH-transcription factors and their modulators.
Erck
C
C
Department of Cell and Molecular Biology, University of Braunschweig, FRG.
Seidl
K
K
D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D024510:Muscle Development; D017570:MyoD Protein / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D011401:Promoter Regions, Genetic; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors