Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin

Leicher Rachel; Ge Eva J.; Lin XingchengReynolds Matthew J.Xie WenjunWalz ThomasZhang BinMuir Tom W.Liu Shixin

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin

【24h】

Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin

机译：Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the "1-3" bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2-chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycombgroup proteins.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America.》 |2020年第48期|30465-30475|共11页
作者
Leicher Rachel; Ge Eva J.; Lin XingchengReynolds Matthew J.Xie WenjunWalz ThomasZhang BinMuir Tom W.Liu Shixin;
展开▼
作者单位

Lab Nanoscale Biophys & Biochem,Rockefeller Univ;

Dept Chem,Princeton Univ;

Dept Chem,MITLab Struct Biophys & Mechanobiol,Rockefeller UnivLab Mol Electron Microscopy,Rockefeller Univ;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Polycomb-group protein; single-molecule force spectroscopy; molecular dynamics simulation; epigenetics; heterochromatin; FREE-ENERGY LANDSCAPE; H3K27 METHYLATION; PRC2 RECRUITMENT; DNA; BINDING; PROTEIN; JARID2; AEBP2; INHIBITION; MECHANISMS;

Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin

摘要

著录项

相关主题

期刊订阅