Histone H2A Mono-Ubiquitination Is a Crucial Step to Mediate PRC1-Dependent Repression of Developmental Genes to Maintain ES Cell Identity

Mitsuhiro Endoh*, Takaho A. Endo, Tamie Endoh, Kyo-ichi Isono, Jafar Sharif, Osamu Ohara, Tetsuro Toyoda, Takashi Ito, Ragnhild Eskeland, Wendy A. Bickmore, Miguel Vidal, Bradley E. Bernstein, Haruhiko Koseki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3), respectively. Compared to H3K27me3, localization and the role of H2AK119u1 are not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.

Original languageEnglish
Article numberARTN e1002774
Number of pages10
JournalPLoS Genetics
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • METHYLTRANSFERASE ACTIVITY
  • RING1B
  • POLYCOMB-GROUP PROTEINS
  • COMPLEX
  • RNA
  • H3
  • X-INACTIVATION
  • CHROMATIN-STRUCTURE
  • EXPRESSION
  • TRANSCRIPTIONAL REGULATORY CIRCUITRY

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