RT Journal Article
SR Electronic
T1 Histone H2AK119 Mono-Ubiquitination is Essential for Polycomb-Mediated Transcriptional Repression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 690461
DO 10.1101/690461
A1 Simone Tamburri
A1 Elisa Lavarone
A1 Daniel Fernández-Pérez
A1 Marika Zanotti
A1 Daria Manganaro
A1 Eric Conway
A1 Diego Pasini
YR 2019
UL http://biorxiv.org/content/early/2019/07/02/690461.abstract
AB The major function of Polycomb group proteins (PcG) is to maintain transcriptional repression to preserve cellular identity. This is exerted by two distinct repressive complexes, PRC1 and PRC2, that modify histones by depositing H2AK119ub1 and H3K27me3, respectively. Both complexes are essential for development and are deregulated in several types of human tumors. PRC1 and PRC2 exist in different variants and show a complex regulatory cross-talk. However, the contribution that H2AK119ub1 plays in mediating PcG repressive functions remains largely controversial. Coupling an inducible system with the expression of a fully catalytic inactive RING1B mutant, we demonstrated that H2AK119ub1 deposition is essential to maintain PcG-target genes repressed in ESC. Loss of H2AK119ub1 induced a rapid displacement of PRC2 activity and a loss of H3K27me3 deposition. This affected both PRC2.1 and PRC2.2 variants and further correlated with a strong displacement and destabilization of canonical PRC1. Finally, we find that variant PRC1 forms can sense H2AK119ub1 deposition, which contributes to their stabilization specifically at sites where this modification is highly enriched. Overall our data place H2AK119ub1 deposition as central hub that mount PcG repressive machineries to preserve cell transcriptional identity.