期刊
NATURE GENETICS
卷 50, 期 10, 页码 1452-+出版社
NATURE RESEARCH
DOI: 10.1038/s41588-018-0218-5
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资金
- European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant) [609989]
- European Union's Horizon 2020 research and innovation programme [676556]
- Spanish Ministry of Economy and Competitiveness [BFU2016-75008-P]
- Centro de Excelencia Severo Ochoa 2013-2017 [SEV-2012-0208]
- AGAUR
- Fundacio 'La Marato de TV3'
- US National Cancer Institute grant [R35CA197569]
- JSPS Research Fellowship for Young Scientists
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.
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