Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor ? target gene activation.

ABSTRACT: Cofactors for estrogen receptor ? (ER?) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ER?-positive cells with 17?-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 ER? 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 ER? after E2 stimulation and that inhibition of either PAD2 or ER? strongly suppresses E2-induced H3R26 citrullination and ER? recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ER?, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3421185 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature