TY - JOUR T1 - Histone H3 Lysine 4 methyltransferases MLL3 and MLL4 Modulate Long-range Chromatin Interactions at Enhancers JF - bioRxiv DO - 10.1101/110239 SP - 110239 AU - Jian Yan AU - Shi-An A Chen AU - Andrea Local AU - Tristin Liu AU - Yunjiang Qiu AU - Ah Young Lee AU - Inkyung Jung AU - Sebastian Preißl AU - Chloe M Rivera AU - Chaochen Wang AU - Haruhiko Ishii AU - Rongxin Fang AU - Zhen Ye AU - Kai Ge AU - Ming Hu AU - Bing Ren Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/21/110239.abstract N2 - 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. ER -