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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation
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Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

机译：在早期肌细胞分化期间与转录共同诱变剂P300相关的基因特异性组蛋白乙酰化曲线

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摘要

Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation. Here, we delineate the functional mode of transcription regulators during early myogenic differentiation using genome-wide chromatin state association. We define a role of transcriptional coactivator p300, when recruited by muscle master regulator MyoD, in the establishment and regulation of myogenic loci at the onset of myoblast differentiation. In addition, we reveal an enrichment of loci-specific histone acetylation at p300 associated active or poised enhancers, particularly when enlisted by MyoD. We provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Our studies present a valuable aptitude for driving condition-specific chromatin state or enhancers pharmacologically to treat muscle-related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development.
机译：通过对远端调节或增强子区域的遗传和表观遗传决定蛋白来施加干细胞分化的分子调节。理解活性或预期增强剂的机械作用因此对干细胞分化的控制是迫切的。基于在致密的增殖肌细胞中的不同表观遗传标记的基因组共同发生，我们先前已经产生了14元染色质状态模型，以在早期肌细胞分化中概述戒指响应作用乙酰化。在这里，我们在利用基因组染色体染色质状态结合时描绘了转录调节剂的功能模式。我们定义转录共同试镜P300的作用，当肌肉大师调节器MyOD招募时，在肌细胞分化的发作时肌菌位的建立和调节。此外，我们揭示了在P300相关的活性或Poived增强剂处的基因特异性组蛋白乙酰化的富集，特别是当由Myod征商时。我们通过Myod在音乐域上通过P300提供新的分子见解。我们的研究表明，用于在药理学上药理学上药物治疗肌肉有关的疾病和鉴定治疗发育的额外肌原毒性靶和分子相互作用的有价值的能力。

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