USE OF A CONDITIONAL MYOD TRANSCRIPTION FACTOR IN STUDIES OF MYOD TRANSACTIVATION AND MUSCLE DETERMINATION
USE OF A CONDITIONAL MYOD TRANSCRIPTION FACTOR IN STUDIES OF MYOD TRANSACTIVATION AND MUSCLE DETERMINATION
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DOI：
10.1073/pnas.90.17.8028
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发表时间：
1993-09-01
影响因子：
11.1
通讯作者：
WEINTRAUB, H
中科院分区：
文献类型：
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作者：
HOLLENBERG, SM;CHENG, PF;WEINTRAUB, H
编码几种类固醇激素受体的结合域的DNA序列与MyoD基因框内融合。当这种嵌合蛋白的基因在NIH 3 T3或10 T1/2成纤维细胞中表达时，这些细胞显示出肌生成依赖性诱导。我们的实验集中在表达雌激素受体-MyoD嵌合体的细胞系上。在雌二醇和蛋白质合成抑制剂放线菌酮的存在下诱导这些细胞系，导致内源性肌细胞生成素基因的激活，但不激活肌肉特异性肌酸激酶或心脏α-肌动蛋白基因。这一结果表明，MyoD不是这些下游生肌基因的“直接”激活剂，但必须首先激活作为中介的生肌蛋白。一旦肌肉被雌激素受体-MyoD诱导，肌肉表型非常稳定，并且不需要雌二醇的持续存在来维持。
DNA sequences encoding the hormone-binding domains of several steroid hormone receptors were fused in frame to the MyoD gene. When the gene for this chimeric protein was expressed in NIH 3T3 or 10T1/2 fibroblasts, these cells displayed hormone-dependent induction of myogenesis. Our experiments focused on cell lines expressing estrogen receptor-MyoD chimeras. Induction of these lines in the presence of estradiol and an inhibitor of protein synthesis, cycloheximide, resulted in the activation of the endogenous myogenin gene but did not activate the muscle-specific creatine kinase or cardiac alpha-actin gene. This result suggests that MyoD is not a ''direct'' activator of these downstream myogenic genes but must first activate myogenin as an intermediary. Once muscle is induced by estrogen receptor-MyoD the muscle phenotype is very stable and does not need the continued presence of estradiol for its maintenance.