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Volume 28, No 11, Nov 2018

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 28 Issue 11, November 2018: 1118-1120

LETTERS TO THE EDITOR

H3K14me3 genomic distributions and its regulation by KDM4 family demethylases

Bin Zhao 1, Wenqi Xu 1, Bowen Rong 1, Guoyu Chen 2, Xuanjia Ye 1,
Ruofei Dai 1, Wenjing Li 1, Jiajia Chen 3, Jiajun Cai 4, Lei Song 5,
Zhao-Qing Luo 5, Rong Zeng 6, Yang Shi 7, Jing-Dong J. Han 2 and Fei Lan 1

1 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Epigenetics and Metabolism, Ministry of Science and Technology, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; 2Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; 3Institutes of Biomedical Sciences and Department of Systems Biology for Medicine, Basic Medical College, Fudan University, Shanghai 20032, China; 4Department of Neurosurgery Huashan Hospital, Fudan University, Shanghai 200040,China; 5Department of Respiratory Medicine, Center of Infection and Immunity, The First Hospital, Jilin University, Changchun, Jilin 130001, China; 6Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China and 7Newborn Medicine Division, Boston Children’s Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA Correspondence: These authors contributed equally: Wenqi Xu, Bowen Rong andGuoyu ChenCorrespondence: Fei Lan (fei_lan@fudan.edu.cn)

Dear Editor,

Histone lysine methylations are essential components of the epigenetic regulatory mechanisms. Although major histone lysine methylations have been extensively investigated, low-abundance methylations remain largely elusive. Among the low-abundance methylations, H3K14me3 has been identified in mammalian cells upon pathological infection by Legionella pneumophila, a gram-negative bacterium and causative agent of a severe form of pneumonia. Global host chromatin H3K14 trimethylation and transcription repression are mediated by an H3K14 methyltransferase, regulator of methylation A (RomA) encoded by the bacterial genome.1 Importantly, previous mass spectrometry studies also suggested the presence of endogenous H3K14 methylations among eukaryotes,2,3,4,5,6,7 although these findings have not been confirmed by independent means. In addition, the genomic distribution as well as the H3K14me3 regulatory enzymes have not been identified. Here, using an H3K14me3-specific antiserum we report the identification of distinct and shared H3K14me3 distribution patterns in HEK293T and human embryonic stem cells (hESCs), two cell lines with extensive epigenome profiles allowing cross comparisons with other known histone marks. H3K14me3 heavily decorates the KRAB-ZNF (Krupple-associated box containing zinc finger gene) clusters in both HEK293T and hESC cells but is only strongly associated with active transcription in HEK293T cells, where it binds thousands of active promoters. We further profiled H3K14me3 in a mouse melanoma cell line, B16, and discovered similar distribution features to those in HEK293T cells. Importantly, we identified members of the KDM4 family of histone demethylases (KDM4A, KDM4B and KDM4C) as H3K14me3 demethylases. As the KDM4 family members have been shown to mediate H3K9me3 and H3K36me3 demethylation,8 our findings also revealed crosstalks among these modifications.


https://doi.org/10.1038/s41422-018-0095-6

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