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The Arginine Methyltransferase PRMT6 Regulates DNA Methylation and Contributes to Global DNA Hypomethylation in Cancer.

Abstract：

:DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and dysregulated in cancer is poorly understood. Here, we show that PRMT6, a protein arginine methyltransferase responsible for asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a), negatively regulates DNA methylation and that PRMT6 upregulation contributes to global DNA hypomethylation in cancer. Mechanistically, PRMT6 overexpression impairs chromatin association of UHRF1, an accessory factor of DNMT1, resulting in passive DNA demethylation. The effect is likely due to elevated H3R2me2a, which inhibits the interaction between UHRF1 and histone H3. Our work identifies a mechanistic link between protein arginine methylation and DNA methylation, which is disrupted in cancer.

journal_name

Cell Rep

journal_title

Cell reports

authors

Veland N,Hardikar S,Zhong Y,Gayatri S,Dan J,Strahl BD,Rothbart SB,Bedford MT,Chen T

doi

10.1016/j.celrep.2017.11.082

subject

Has Abstract

pub_date

2017-12-19 00:00:00

pages

3390-3397

issue

12

issn

2211-1247

pii

S2211-1247(17)31749-7

journal_volume

21

pub_type

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