2. Academic Validation
  3. Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

  • Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7717-E7726. doi: 10.1073/pnas.1706831114.
Haolin Liu 1 2 3,  Chao Wang 1 2,  Schuyler Lee 1 2,  Yu Deng 4,  Matthew Wither 5,  Sangphil Oh 6,  Fangkun Ning 1 2,  Carissa Dege 1 2,  Qianqian Zhang 7,  Xinjian Liu 4,  Aaron M Johnson 5,  Jianye Zang 8,  Zhongzhou Chen 7,  Ralf Janknecht 6,  Kirk Hansen 5,  Philippa Marrack 1 2 3 5,  Chuan-Yuan Li 4,  John W Kappler 9 2 3,  James Hagman 9 2 5,  Gongyi Zhang 9 2
Affiliations

Affiliations

  • 1 Department of Biomedical Research, National Jewish Health, Denver, CO 80206.
  • 2 Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Denver, CO 80206.
  • 3 Howard Hughes Medical Institute, Denver, CO 80206.
  • 4 Department of Dermatology, Duke University, Durham, NC 27710.
  • 5 Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80216.
  • 6 Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
  • 7 State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
  • 8 Department of Molecular Biology, University of Science and Technology of China, Hefei 900015, People's Republic of China.
  • 9 Department of Biomedical Research, National Jewish Health, Denver, CO 80206; kapplerj@njhealth.org hagmanj@njhealth.org ZhangG@NJHealth.org.
PMID: 28847961 DOI: 10.1073/pnas.1706831114
Abstract

Two of the unsolved, important questions about Epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-containing proteins, JMJD5 and JMJD7, have divalent cation-dependent Protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 and JMJD7, acting as aminopeptidases, progressively digest the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones. Furthermore, depletion of JMJD7 in breast Cancer cells greatly decreases cell proliferation. The Protease activities of JMJD5 and JMJD7 represent a mechanism for removal of histone tails bearing methylated arginine residues and define a potential mechanism of transcription regulation.

Keywords

JMJD5/7; arginine methylation; clipping; histone tail.

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