Myc influences global chromatin structure
Myc influences global chromatin structure
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DOI：
10.1038/sj.emboj.7601152
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
Eisenman, Robert N.
中科院分区：
文献类型：
--
作者：
Knoepfler, Paul S.;Zhang, Xiao-yong;Eisenman, Robert N.
myc原癌基因家族编码转录因子（c-、N-和L-Myc），这些转录因子调节细胞生长和增殖，并参与多种癌症的病因。Myc蛋白被认为通过结合和调节特定的靶基因发挥作用。在这里，我们报告Myc蛋白是广泛维持活性染色质所必需的。神经元祖细胞和其他细胞类型中N- myc的破坏导致核浓缩，并伴随着与染色质失活相关的组蛋白修饰的大规模变化，包括低乙酰化和甲基化改变。这些作用在很大程度上被外源性Myc和分化逆转，并被Myc拮抗剂Mad1模仿。第一个染色质变化在Myc丢失6小时内明显，并导致染色质结构的变化。Myc广泛影响染色质，部分通过上调组蛋白乙酰转移酶GCN5。这项研究提供了肿瘤蛋白调控整体染色质结构的第一个证据，并可能解释Myc对细胞行为和肿瘤发生的广泛影响。
The family of myc proto-oncogenes encodes transcription factors ( c- ,N-, and L-Myc) that regulate cell growth and proliferation and are involved in the etiology of diverse cancers. Myc proteins are thought to function by binding and regulating specific target genes. Here we report that Myc proteins are required for the widespread maintenance of active chromatin. Disruption of N- myc in neuronal progenitors and other cell types leads to nuclear condensation accompanied by large-scale changes in histone modifications associated with chromatin inactivation, including hypoacetylation and altered methylation. These effects are largely reversed by exogenous Myc as well as by differentiation and are mimicked by the Myc antagonist Mad1. The first chromatin changes are evident within 6 h of Myc loss and lead to changes in chromatin structure. Myc widely influences chromatin in part through upregulation of the histone acetyltransferase GCN5. This study provides the first evidence for regulation of global chromatin structure by an oncoprotein and may explain the broad effects of Myc on cell behavior and tumorigenesis.