| Literature DB >> 27058665 |
Hongjie Shen1, Wenqi Xu1, Rui Guo2, Bowen Rong2, Lei Gu3, Zhentian Wang2, Chenxi He2, Lijuan Zheng2, Xin Hu4, Zhen Hu4, Zhi-Ming Shao4, Pengyuan Yang5, Feizhen Wu2, Yujiang Geno Shi6, Yang Shi7, Fei Lan8.
Abstract
Regulation of enhancer activity is important for controlling gene expression programs. Here, we report that a biochemical complex containing a potential chromatin reader, RACK7, and the histone lysine 4 tri-methyl (H3K4me3)-specific demethylase KDM5C occupies many active enhancers, including almost all super-enhancers. Loss of RACK7 or KDM5C results in overactivation of enhancers, characterized by the deposition of H3K4me3 and H3K27Ac, together with increased transcription of eRNAs and nearby genes. Furthermore, loss of RACK7 or KDM5C leads to de-repression of S100A oncogenes and various cancer-related phenotypes. Our findings reveal a RACK7/KDM5C-regulated, dynamic interchange between histone H3K4me1 and H3K4me3 at active enhancers, representing an additional layer of regulation of enhancer activity. We propose that RACK7/KDM5C functions as an enhancer "brake" to ensure appropriate enhancer activity, which, when compromised, could contribute to tumorigenesis.Entities:
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Year: 2016 PMID： 27058665 PMCID： PMC4826479 DOI： 10.1016/j.cell.2016.02.064
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582