Molinari S, Relaix F, Lemonnier M, Kirschbaum B, Schäfer B, Buckingham M
CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75724 Paris Cedex 15, France.
Mol Cell Biol. 2004 Apr;24(7):2944-57. doi: 10.1128/MCB.24.7.2944-2957.2004.
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.
小鼠心肌肌动蛋白基因的表达依赖于一个远端增强子（-7千碱基对），在转基因小鼠中，该增强子已被证明可将表达导向胚胎骨骼肌。这个远端序列的存在也与心肌肌动蛋白转基因的可重复性表达相关。在分化的骨骼肌细胞中，增强子的活性由一个E框驱动，该E框结合MyoD家族成员，还由一个位于DNase I超敏位点位置的富含3'端AT的序列驱动。这个序列不直接结合MEF2蛋白或其他已知的肌肉转录因子。Oct1和Emb（一种VI类POU结构域蛋白）与DNA上的共有位点结合，而Emb的结合对活性很重要。Emb作为主要复合物与MEF2D和组蛋白转乙酰酶p300结合。在这种复合物中以及作为肌肉细胞提取物中的主要形式存在的Emb形式比先前描述的更长（80 kDa）。这些结果证明了这种新型复合物在心肌肌动蛋白基因转录调控中的重要性，并暗示其在与肌肉基因激活相关的染色质重塑中可能发挥的作用。
