RT Journal Article
SR Electronic
T1 Histone H3 Lysine 4 methyltransferases MLL3 and MLL4 Modulate Long-range Chromatin Interactions at Enhancers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 110239
DO 10.1101/110239
A1 Jian Yan
A1 Shi-An A Chen
A1 Andrea Local
A1 Tristin Liu
A1 Yunjiang Qiu
A1 Ah Young Lee
A1 Inkyung Jung
A1 Sebastian Preißl
A1 Chloe M Rivera
A1 Chaochen Wang
A1 Haruhiko Ishii
A1 Rongxin Fang
A1 Zhen Ye
A1 Kai Ge
A1 Ming Hu
A1 Bing Ren
YR 2017
UL http://biorxiv.org/content/early/2017/02/21/110239.abstract
AB Regulation of gene expression in mammalian cells depends on long-range chromatin interactions between enhancers and promoters. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here we show that the histone H3 Lysine 4 monomethylation (H3K4me1) writer proteins 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 MLL3/4 leads to greatly reduced frequencies of chromatin interactions and failure of lineage-specific gene expression programs. We further show that H3K4me1 facilitates recruitment of the Cohesin complex to chromatin in vitro and in vivo, providing a potential mechanism for MLL3/4 to promote chromatin looping. Taken together, our results support an active role for MLL3/4 in modulating chromatin organization at enhancers in mammalian cells.