Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors

被引：702

作者：

Mohn, Fabio ^{[1
]}

Weber, Michael ^{[1
]}

Rebhan, Michael ^{[1
]}

Roloff, Tim C. ^{[1
]}

Richter, Jens ^{[2
]}

Stadler, Michael B. ^{[1
]}

Bibel, Miriam ^{[2
]}

Schuebeler, Dirk ^{[1
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[2] Novartis Inst Biomed Res, Neurodegenerat Dept, Neurosci Res, CH-4002 Basel, Switzerland

来源：

MOLECULAR CELL | 2008年 / 30卷 / 06期

关键词：

D O I：

10.1016/j.molcel.2008.05.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cellular differentiation entails loss of pluripotency and gain of lineage- and cell-type-specific characteristics. Using a murine system that progresses from stem cells to lineage-committed progenitors to terminally differentiated neurons, we analyzed DNA methylation and Polycomb-mediated histone H3 methylation (H3K27me3). We show that several hundred promoters, including pluripotency and germline-specific genes, become DNA methylated in lineage-committed progenitor cells, suggesting that DNA methylation may already repress pluripotency in progenitor cells. Conversely, we detect loss and acquisition of H3K27me3 at additional targets in both progenitor and terminal states. Surprisingly, many neuron-specific genes that become activated upon terminal differentiation are Polycomb targets only in progenitor cells. Moreover, promoters marked by H3K27me3 in stem cells frequently become DNA methylated during differentiation, suggesting context-dependent crosstalk between Polycomb and DNA methylation. These data suggest a model how de novo DNA methylation and dynamic switches in Polycomb targets restrict pluripotency and define the developmental potential of progenitor cells.

引用

页码：755 / 766

页数：12

共 68 条

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