A novel complex regulates cardiac actin gene expression through interaction of Emb, a class VI POU domain protein, MEF2D, and the histone transacetylase p300.
Expression of the mouse cardiac actin gene depends on a distal enhancer (-7 kbp) which has been shown, in transgenic mice, to direct expression to embryonic skeletal muscle. The presence of this distal sequence is also associated with reproducible expression of cardiac actin transgenes. In differentiated skeletal muscle cells, activity of the enhancer is driven by an E box, binding MyoD family members, and by a 3' AT-rich sequence which is in the location of a DNase I-hypersensitive site. This sequence does not bind MEF2 proteins, or other known muscle transcription factors, directly. Oct1 and Emb, a class VI POU domain protein, bind to consensus sites on the DNA, and it is the binding of Emb which is important for activity. Emb binds as a major complex with MEF2D and the histone transacetylase p300. The form of Emb present in this complex and as a major form in muscle cell extracts is longer (80 kDa) than that previously described. These results demonstrate the importance of this novel complex in the transcriptional regulation of the cardiac actin gene and suggest a potential role in chromatin remodeling associated with muscle gene activation.
Molinari
S
S
CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France.
Relaix
F
F
Lemonnier
M
M
Kirschbaum
B
B
Schäfer
B
B
Buckingham
M
M
D000123:Acetyltransferases / Q000378:metabolism*; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D046911:Macromolecular Substances; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D000199:Actins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D064326:MEF2 Transcription Factors; D046911:Macromolecular Substances; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C578044:Mef2d protein, mouse