Abstract:
:Long-range chromatin interactions between enhancers and promoters are essential for transcription of many developmentally controlled genes in mammals and other metazoans. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here, we show that the enhancer-specific histone H3 lysine 4 monomethylation (H3K4me1) and the histone methyltransferases MLL3 and MLL4 (MLL3/4) play an active role in this process. We demonstrate that in differentiating mouse embryonic stem cells, MLL3/4-dependent deposition of H3K4me1 at enhancers correlates with increased levels of chromatin interactions, whereas loss of this histone modification leads to reduced levels of chromatin interactions and defects in gene activation during differentiation. H3K4me1 facilitates recruitment of the Cohesin complex, a known regulator of chromatin organization, to chromatin in vitro and in vivo, providing a potential mechanism for MLL3/4 to promote chromatin interactions between enhancers and promoters. Taken together, our results support a role for MLL3/4-dependent H3K4me1 in orchestrating long-range chromatin interactions at enhancers in mammalian cells.
journal_name
Cell Resjournal_title
Cell researchauthors
Yan J,Chen SA,Local A,Liu T,Qiu Y,Dorighi KM,Preissl S,Rivera CM,Wang C,Ye Z,Ge K,Hu M,Wysocka J,Ren Bdoi
10.1038/cr.2018.1subject
Has Abstractpub_date
2018-02-01 00:00:00pages
204-220issue
2eissn
1001-0602issn
1748-7838pii
cr20181journal_volume
28pub_type
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