Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site
Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site
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DOI：
10.1073/pnas.95.24.14220
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Maire, P
中科院分区：
文献类型：
--
作者：
Spitz, F;Demignon, J;Maire, P
Myogenin是MyoD蛋白家族中的一员，在体内的成肌细胞融合过程中，Myogenin在体内的早期表达。先前对转基因小鼠的研究表明，一个184 bp的肌原启动子片段足以在胚胎发生过程中正确驱动β -半乳糖苷酶转基因的表达。我们在这里表明，该区域存在的DNA基序之一MEF3基序的突变，取消了该β -半乳糖苷酶转基因的正确表达。我们发现与MEF3位点结合的蛋白是Six/sine oculis家族的同源蛋白。特异性针对Six1或Six4蛋白的抗体表明，当肌原蛋白被激活时，胚胎中存在这两种蛋白，并在成人肌肉核提取物中形成肌肉特异性mef3结合活性。这两种蛋白都在C2C12肌原细胞的细胞核中积累，瞬时转染实验证实Six1和Six4能够反激活含有MEF3位点的报告基因。总之，这些结果确定了六种同源蛋白作为转录因子家族，通过激活其中一个关键调节因子，肌生成素来控制肌肉的形成。
Myogenin, one of the MyoD family of proteins, is expressed early during somitogenesis and is required for myoblast fusion in vivo. Previous studies in transgenic mice have shown that a 184-bp myogenin promoter fragment is sufficient to correctly drive expression of a beta-galactosidase transgene during embryogenesis. We show here that mutation of one of the DNA motifs present in this region, the MEF3 motif, abolished correct expression of this beta-galactosidase transgene. We have found that the proteins that bind to the MEF3 site are homeoproteins of the Six/sine oculis family. Antibodies directed specifically against Six1 or Six4 proteins reveal that each of these proteins is present in the embryo when myogenin is activated and constitutes a muscle-specific MEF3-binding activity in adult muscle nuclear extracts. Both of these proteins accumulate in the nucleus of C2C12 myogenic cells, and transient transfection experiments confirm that Six1 and Six4 are able to transactivate a reporter gene containing MEF3 sites. Altogether these results establish Six homeoproteins as a family of transcription factors controlling muscle formation through activation of one of its key regulators, myogenin.