Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila
Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila
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DOI：
10.1101/gad.1352305
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发表时间：
2005-12-15
影响因子：
10.5
通讯作者：
Cole, MD
中科院分区：
文献类型：
--
作者：
Goodliffe, JM;Wieschaus, E;Cole, MD
Myc癌蛋白的异常积累促进增殖并诱导癌发生。然而，在正常细胞中，丰富的Myc蛋白抑制c-myc基因座的转录。癌细胞通常会失去这种自我抑制。我们研究了果蝇中myc的控制，并在这里显示，果蝇的直系同源物，dmyc，也经历autorepression。我们发现，发育抑制物Polycomb（Pc）是所需的dmyc autorepression，这Pc-dMye介导的抑制蔓延在一个875 kb的区域，包括dmyc基因。为了进一步研究Myc和Polycomb之间的关系，我们使用微阵列来识别由每一个调控的基因，并确定两者之间的惊人关系：一组大的dMyc激活靶点通常被Pc抑制，73%的dMyc抑制靶点需要Pc进行这种抑制。染色质免疫沉淀证实，许多dMyc-Pc-阻遏位点具有由Pc识别的表观遗传标记。我们的研究结果表明，Myc和Polycomb之间的一种新的关系，其中Myc增强Polycomb抑制，以抑制目标，和Myc抑制Polycomb抑制，以激活目标。
Aberrant accumulation of the Myc oncoprotein propels proliferation and induces carcinogenesis. In normal cells, however, an abundance of Myc protein represses transcription at the c-myc locus. Cancer cells often lose this autorepression. We examined the control of myc in Drosophila and show here that the Drosophila ortholog, dmyc, also undergoes autorepression. We find that the developmental repressor Polycomb (Pc) is required for dmyc autorepression, and that this Pc-dMye-mediated repression spreads across an 875-kb region encompassing the dmyc gene. To further investigate the relationship between Myc and Polycomb, we used microarrays to identify genes regulated by each, and identify a striking relationship between the two: A large set of dMyc activation targets is normally repressed by Pc, and 73% of dMyc repression targets require Pc for this repression. Chromatin immunoprecipitation confirmed that many dMyc-Pc-repressed loci have an epigenetic mark recognized by Pc. Our results suggest a novel relationship between Myc and Polycomb, wherein Myc enhances Polycomb repression in order to repress targets, and Myc suppresses Polycomb repression in order to activate targets.