TY - JOUR
T1 - Methylation of H2AR29 is a novel repressive PRMT6 target
AU - Waldmann, Tanja
AU - Izzo, Annalisa
AU - Kamieniarz, Kinga
AU - Richter, Florian
AU - Vogler, Christine
AU - Sarg, Bettina
AU - Lindner, Herbert
AU - Young, Nicolas L.
AU - Mittler, Gerhard
AU - Garcia, Benjamin A.
AU - Schneider, Robert
N1 - Funding Information:
Work in the RS laboratory is supported by the Max Planck Society, the DFG (SFB 746) and an ERC starting grant. We are grateful to F Kappes (University of Michigan) for the PRMT knockdown cell lines.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960554565&partnerID=8YFLogxK
U2 - 10.1186/1756-8935-4-11
DO - 10.1186/1756-8935-4-11
M3 - Article
AN - SCOPUS:79960554565
VL - 4
JO - Epigenetics and Chromatin
JF - Epigenetics and Chromatin
SN - 1756-8935
IS - 1
M1 - 11
ER -