Whole-genome analysis of muscle founder cells implicates the chromatin regulator Sin3A in muscle identity.

Whole-genome analysis of muscle founder cells implicates the chromatin regulator Sin3A in muscle identity.
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DOI:
10.1016/j.celrep.2014.07.005
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发表时间:
2014-08-07
期刊:
影响因子:
8.8
通讯作者:
Baylies MK
Baylies MK
中科院分区:
生物学1区
文献类型:
--
作者:
Dobi KC;Halfon MS;Baylies MK

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骨骼肌有多种形状和大小,这种多样性会影响功能和疾病易感性。为了了解肌肉多样性是如何产生的,我们对果蝇胚胎的两个肌肉亚群进行了基因表达谱分析。通过比较这些亚集的转录图谱,我们确定了一个核心的方正细胞丰富的基因群。我们筛选了肌肉缺陷的突变体,并确定了Sin3A和其他10个转录和染色质调节因子在果蝇胚胎体细胞肌肉中的新功能。Sin3A是肌肉亚群形态发生所必需的,而Sin3A突变体表现为肌肉丢失和错位附着。此外,在Sin3A杂合子胚胎中,识别基因转录因子的错误表达会导致一块肌肉直接转化为另一块肌肉,而Sin3A的过度表达会导致反向转化。我们的数据表明,Sin3A是一个关键缓冲区,在肌肉身份形成过程中控制肌肉对转录因子的反应,从而产生组织多样性。
Skeletal muscles are formed in numerous shapes and sizes, and this diversity impacts function and disease susceptibility. To understand how muscle diversity is generated, we performed gene expression profiling of two muscle subsets from Drosophila embryos. By comparing the transcriptional profiles of these subsets, we identified a core group of founder cell-enriched genes. We screened mutants for muscle defects and identified novel functions for Sin3A and 10 other transcription and chromatin regulators in the Drosophila embryonic somatic musculature. Sin3A is required for the morphogenesis of a musclesubset, and Sin3A mutants display muscle loss and misattachment. Additionally, misexpression of identity gene transcription factors in Sin3A heterozygous embryos leads to direct transformations of one muscle into another, while overexpression of Sin3A results in the reverse transformation. Our data implicate Sin3A as a keybuffer controlling muscle responsiveness to transcription factors in the formation of muscle identity, thereby generating tissue diversity.
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