Histone H3 lysine 4 monomethylation modulates long- range chromatin interactions at enhancers  

作　　者：Jian Yan Shi-An A Chen Andrea Local Tristin Liu Yunjiang Qiu Kristel M Dorighi Sebastian Preissl Chloe M Rivera Chaochen Wang Zhen Ye Kai Ge Ming Hu Joanna Wysocka Bing Ren 

机构地区：[1]Ludwig Institute for Cancer Research, 9500 Gilman Dr., La Jolla, CA 92093, USA [2]Department of Medical Biochemistry and Biophysics, Division of Functional Genomics and Systems Biology, Karolinska Institutet, 171 65 Stockholm, Sweden [3]Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA [4]Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA [5]Department of Cellular and Molecular Medicine, University of California San Diego, School of Medicine, Institute of Genomic Medicine, 9500 Gilman Dr., La Jolla, CA 92093, USA [6]Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA

出　　处：《Cell Research》2018年第2期204-220,共17页细胞研究（英文版）

摘　　要：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 （H3K4mel） 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 H3K4mel 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. H3K4mel 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 H3K4mel in orchestrating long-range ehromatin interactions at enhancers in mammalian cells.

关 键 词：ENHANCER H3K4mel MLL3 MLL4 chromatin loop 

分 类 号：Q243[生物学—细胞生物学] TQ460.4[化学工程—制药化工]