Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation.
Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation.
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DOI：
10.1371/journal.pone.0245618
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Davie J
中科院分区：
文献类型：
--
作者：
Adhikari A;Kim W;Davie J
骨骼肌基因表达受生肌调节家族(MRF)的调控，其中包括MyoD(MYOD1)和Mygenin(MYOG)。众所周知，MYOD1和MYOG可以调节一组重叠的肌肉基因，但MYOD1不能弥补体内MYOG的缺失。在体外，晚期肌肉基因已被证明与这两个因素结合，但需要MYOG才能激活。这一要求的分子基础尚不清楚。我们在这里证明了MYOG是TBP和RNAPII招募到肌肉基因启动子所必需的，这表明MYOG在组装转录机制中是必不可少的。由MYOD1和MYOG调控的基因包括肌肉融合所需的基因、肌构体和肌构体，我们发现肌构体完全依赖于MYOG的激活。我们还试图确定MYOD1在MYOG依赖的基因激活中的作用，并意外地发现MYOG是维持Myod1表达所必需的。然而，我们也发现，外源MYOD1不能补偿Myog的丢失和激活肌肉基因的表达。因此，我们的结果表明，MYOD1和MYOG以前馈的方式维持彼此的表达，同时也表明，在这两个因子结合的晚期肌肉基因启动子上，需要装载TBP并激活基因表达的是MYOG，而不是MYOD1。
Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.
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