TY - JOUR
T1 - XHira-dependent histone H3.3 deposition facilitates prc2 recruitment at developmental loci in ES cells
AU - Banaszynski, Laura A.
AU - Wen, Duancheng
AU - Dewell, Scott
AU - Whitcomb, Sarah J.
AU - Lin, Mingyan
AU - Diaz, Nichole
AU - Elsässer, Simon J.
AU - Chapgier, Ariane
AU - Goldberg, Aaron D.
AU - Canaani, Eli
AU - Rafii, Shahin
AU - Zheng, Deyou
AU - Allis, C. David
N1 - Funding Information:
This work was supported by The Rockefeller University Fund (to C.D.A.), Tri-Institutional Stem Cell Initiative (to C.D.A. and S.R.), US National Institute of Mental Health (MH087840 and MH073164 to D.Z.), Damon Runyon Cancer Research Foundation (L.A.B.), and The Rockefeller University Women & Science Initiative (L.A.B.). We thank I. Falciatori for help with the teratoma assay, Y. Zhang for purified recombinant PRC2 complex, and S. Chen and Y. Shi for the Jmjd3 antibody. The Troma-I hybridoma developed by P. Brulet and R. Kemler was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biology at The University of Iowa. We thank L. Baker, E. Korb, E. Duncan, and C. Lu for critical reading of this manuscript and J. Wysocka and members of the Allis lab for helpful discussions.
PY - 2013/9/26
Y1 - 2013/9/26
N2 - Summary Polycomb repressive complex 2 (PRC2) regulates gene expression during lineage specification through trimethylation of lysine 27 on histone H3 (H3K27me3). In Drosophila, polycomb binding sites are dynamic chromatin regions enriched with the histone variant H3.3. Here, we show that, in mouse embryonic stem cells (ESCs), H3.3 is required for proper establishment of H3K27me3 at the promoters of developmentally regulated genes. Upon H3.3 depletion, these promoters show reduced nucleosome turnover measured by deposition of de novo synthesized histones and reduced PRC2 occupancy. Further, we show H3.3-dependent interaction of PRC2 with the histone chaperone, Hira, and that Hira localization to chromatin requires H3.3. Our data demonstrate the importance of H3.3 in maintaining a chromatin landscape in ESCs that is important for proper gene regulation during differentiation. Moreover, our findings support the emerging notion that H3.3 has multiple functions in distinct genomic locations that are not always correlated with an "active" chromatin state.
AB - Summary Polycomb repressive complex 2 (PRC2) regulates gene expression during lineage specification through trimethylation of lysine 27 on histone H3 (H3K27me3). In Drosophila, polycomb binding sites are dynamic chromatin regions enriched with the histone variant H3.3. Here, we show that, in mouse embryonic stem cells (ESCs), H3.3 is required for proper establishment of H3K27me3 at the promoters of developmentally regulated genes. Upon H3.3 depletion, these promoters show reduced nucleosome turnover measured by deposition of de novo synthesized histones and reduced PRC2 occupancy. Further, we show H3.3-dependent interaction of PRC2 with the histone chaperone, Hira, and that Hira localization to chromatin requires H3.3. Our data demonstrate the importance of H3.3 in maintaining a chromatin landscape in ESCs that is important for proper gene regulation during differentiation. Moreover, our findings support the emerging notion that H3.3 has multiple functions in distinct genomic locations that are not always correlated with an "active" chromatin state.
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U2 - 10.1016/j.cell.2013.08.061
DO - 10.1016/j.cell.2013.08.061
M3 - Article
C2 - 24074864
AN - SCOPUS:84884865693
SN - 0092-8674
VL - 155
SP - X107-120
JO - Cell
JF - Cell
IS - 1
ER -