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Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2. 2016

Sarah Cooper, and Anne Grijzenhout, and Elizabeth Underwood, and Katia Ancelin, and Tianyi Zhang, and Tatyana B Nesterova, and Burcu Anil-Kirmizitas, and Andrew Bassett, and Susanne M Kooistra, and Karl Agger, and Kristian Helin, and Edith Heard, and Neil Brockdorff

Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood. Here we demonstrate a critical role for the PRC2 cofactor Jarid2 in mediating the interaction of PRC2 with H2AK119u1. We identify a ubiquitin interaction motif at the amino-terminus of Jarid2, and demonstrate that this domain facilitates PRC2 localization to H2AK119u1 both in vivo and in vitro. Our findings ascribe a critical function to Jarid2 and define a key mechanism that links PRC1 and PRC2 in the establishment of Polycomb domains.