Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment
| Autor: | Cooper, Sarah, Dienstbier, Martin, Hassan, Raihann, Schermelleh, Lothar, Sharif, Jafar, Blackledge, Neil P., De Marco, Valeria, Elderkin, Sarah, Koseki, Haruhiko, Klose, Robert, Heger, Andreas, Brockdorff, Neil |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Molecular Sequence Data
Polycomb Repressive Complex 2 Ubiquitination macromolecular substances DNA Methylation Article Cell Line Protein Structure Tertiary Histones Mice lcsh:Biology (General) Heterochromatin Animals CpG Islands Amino Acid Sequence lcsh:QH301-705.5 Embryonic Stem Cells Protein Binding |
| Zdroj: | Cell Reports, Vol 7, Iss 5, Pp 1456-1470 (2014) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs), CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications. Graphical Abstract Highlights • Absence of DNA methylation recruits Polycomb complexes to pericentric heterochromatin • H3K9me3 antagonizes activity of PRC2, but not PRC1, at pericentric heterochromatin • CpG density and antagonism by H3 modifications define genome-wide Polycomb occupancy • PRC1-mediated H2AK119u1 recruits PRC2 and H3K27me3 Polycomb group proteins are important repressors of developmentally regulated genes, but how these complexes are recruited to their target genes is still largely unknown. In this study, Cooper et al. show that Polycomb group protein recruitment is a combinatorial readout of unmethylated CpG density and antagonism by specific histone tail modifications. Unexpectedly, they also show that monoubiquitylated histone H2A, the modification produced by Polycomb repressor complex 1 (PRC1), is sufficient to recruit PRC2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|