Peptidylarginine Deiminase 2-catalyzed Histone H3 Arginine 26 Citrullination Facilitates Estrogen Receptor α Target Gene Activation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Aug 3

PMID 22853951

Citations 116

Authors

Xuesen Zhang

Michael Bolt

Michael J Guertin

Wei Chen

Sheng Zhang

Brian D Cherrington

Daniel J Slade

Christina J Dreyton

Venkataraman Subramanian

Kevin L Bicker

Paul R Thompson

Michael A Mancini

John T Lis

Scott A Coonrod

Affiliations

Soon will be listed here.

Abstract

Cofactors for estrogen receptor α (ERα) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ERα-positive cells with 17β-estradiol (E2) promotes global citrullination of histone H3 arginine 26 (H3R26) on chromatin. Additionally, we found that the H3 citrulline 26 (H3Cit26) modification colocalizes with ERα at decondensed chromatin loci surrounding the estrogen-response elements of target promoters. Surprisingly, we also found that citrullination of H3R26 is catalyzed by peptidylarginine deiminase (PAD) 2 and not by PAD4 (which citrullinates H4R3). Further, we showed that PAD2 interacts with ERα after E2 stimulation and that inhibition of either PAD2 or ERα strongly suppresses E2-induced H3R26 citrullination and ERα recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ERα, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.

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