» Articles » PMID: 21774791

Methylation of H2AR29 is a Novel Repressive PRMT6 Target

Overview
Publisher Biomed Central
Specialties Biochemistry
Genetics
Date 2011 Jul 22
PMID 21774791
Citations 47
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Covalent histone modifications are central to all DNA-dependent processes. Modifications of histones H3 and H4 are becoming well characterised, but knowledge of how H2A modifications regulate chromatin dynamics and gene expression is still very limited.

Results: To understand the function of H2A modifications, we performed a systematic analysis of the histone H2A methylation status. We identified and functionally characterised two new methylation sites in H2A: R11 (H2AR11) and R29 (H2AR29). Using an unbiased biochemical approach in combination with candidate assays we showed that protein arginine methyltransferase (PRMT) 1 and PRMT6 are unique in their ability to catalyse these modifications. Importantly we found that H2AR29me2 is specifically enriched at genes repressed by PRMT6, implicating H2AR29me2 in transcriptional repression.

Conclusions: Our data establishes R11 and R29 as new arginine methylation sites in H2A. We identified the specific modifying enzymes involved, and uncovered a novel functional role of H2AR29me2 in gene silencing in vivo. Thus this work reveals novel insights into the function of H2A methylation and in the mechanisms of PRMT6-mediated transcriptional repression.

Citing Articles

Assessment of PRMT6-dependent alternative splicing in pluripotent and differentiating NT2/D1 cells.

Eudenbach M, Busam J, Bouchard C, Rossbach O, Zarnack K, Bauer U Life Sci Alliance. 2025; 8(4).

PMID: 39900436 PMC: 11791029. DOI: 10.26508/lsa.202402946.


The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy.

Hong J, Li X, Hao Y, Xu H, Yu L, Meng Z Cell Death Differ. 2024; 31(11):1561-1575.

PMID: 39134684 PMC: 11519485. DOI: 10.1038/s41418-024-01357-8.


Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease.

Zhang Y, Wei S, Jin E, Jo Y, Oh C, Bae G Diabetes Metab J. 2024; 48(4):487-502.

PMID: 39043443 PMC: 11307121. DOI: 10.4093/dmj.2023.0362.


Dysregulation of arginine methylation in tumorigenesis.

Li X, Song Y, Mu W, Hou X, Ba T, Ji S Front Mol Biosci. 2024; 11:1420365.

PMID: 38911125 PMC: 11190088. DOI: 10.3389/fmolb.2024.1420365.


PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt-β-catenin pathway.

Yu P, Xu T, Ma W, Fang X, Bao Y, Xu C J Exp Clin Cancer Res. 2024; 43(1):116.

PMID: 38637831 PMC: 11025288. DOI: 10.1186/s13046-024-03038-3.


References
1.
Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

2.
Sultan M, Schulz M, Richard H, Magen A, Klingenhoff A, Scherf M . A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008; 321(5891):956-60. DOI: 10.1126/science.1160342. View

3.
Schurter B, Koh S, Chen D, Bunick G, Harp J, Hanson B . Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry. 2001; 40(19):5747-56. DOI: 10.1021/bi002631b. View

4.
Bedford M, Clarke S . Protein arginine methylation in mammals: who, what, and why. Mol Cell. 2009; 33(1):1-13. PMC: 3372459. DOI: 10.1016/j.molcel.2008.12.013. View

5.
Lee J, Cook J, Yang Z, Mirochnitchenko O, Gunderson S, Felix A . PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem. 2004; 280(5):3656-64. DOI: 10.1074/jbc.M405295200. View