@article{6b38e722edec492cbad761ec8f10de95,
title = "Promoter bivalency favors an open chromatin architecture in embryonic stem cells",
abstract = "In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.",
author = "Gl{\`o}ria Mas and Enrique Blanco and Cecilia Ballar{\'e} and Miriam Sans{\'o} and Spill, {Yannick G.} and Deqing Hu and Yuki Aoi and {Le Dily}, Fran{\c c}ois and Ali Shilatifard and Marti-Renom, {Marc A.} and {Di Croce}, Luciano",
note = "Funding Information: This work would not have been possible without F. Stewart and M. Obst (Biotechnology Center, TU Dresden, Germany), who generously provided the C57B1/6 Mll2F/F mouse ESCs. We are indebted to L. Morey and members of the Di Croce laboratory for insightful discussions and critical reading of the manuscript. We thank V. A. Raker for scientific editing, and the CRG Genomics Unit for their help in genomic experiments. This work was partially supported by the European Research Council under the 7th Framework Program FP7/2007–2013 (ERC grant agreement 609989) and the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement 676556) to M.A.M.-R. We also acknowledge support of the Spanish Ministry of Economy and Competitiveness (BFU2016-75008-P), Centro de Excelencia Severo Ochoa 2013–2017 (SEV-2012-0208), AGAUR, and Fundaci{\'o} {\textquoteleft}La Marat{\'o} de TV3{\textquoteright} to L.D.C. We also acknowledge a JSPS Research Fellowship for Young Scientists to support Y.A. of US National Cancer Institute grant R35CA197569 to A.S.H. Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2018",
month = oct,
day = "1",
doi = "10.1038/s41588-018-0218-5",
language = "English (US)",
volume = "50",
pages = "1452--1462",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",
}