期刊
EMBO JOURNAL
卷 25, 期 12, 页码 2723-2734出版社
WILEY
DOI: 10.1038/sj.emboj.7601152
关键词
chromatin; epigenetics; histone modification; Myc; stem and progenitor cells
资金
- NCI NIH HHS [R01 CA020525, R37 CA020525, K01CA114400-01, CA20525] Funding Source: Medline
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.
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