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

dc.contributor.authorZhang, Xuesenen
dc.contributor.authorBolt, Michaelen
dc.contributor.authorGuertin, Michael J.en
dc.contributor.authorChen, Weien
dc.contributor.authorZhang, Shengen
dc.contributor.authorCherrington, Brian D.en
dc.contributor.authorSlade, Daniel J.en
dc.contributor.authorDreyton, Christina J.en
dc.contributor.authorSubramanian, Venkataramanen
dc.contributor.authorBicker, Kevin L.en
dc.contributor.authorThompson, Paul R.en
dc.contributor.authorMancini, Michael A.en
dc.contributor.authorLis, John T.en
dc.contributor.authorCoonrod, Scott A.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentCenter for Drug Discoveryen
dc.date.accessioned2016-11-09T03:19:56Zen
dc.date.available2016-11-09T03:19:56Zen
dc.date.issued2012-08-14en
dc.description.abstractCofactors 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.en
dc.description.versionPublished versionen
dc.format.extent13331 - 13336 page(s)en
dc.identifier.doihttps://doi.org/10.1073/pnas.1203280109en
dc.identifier.issn0027-8424en
dc.identifier.issue33en
dc.identifier.urihttp://hdl.handle.net/10919/73410en
dc.identifier.volume109en
dc.language.isoenen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000307807000045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titlePeptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor alpha target gene activationen
dc.title.serialProceedings of The National Academy of Sciences of The United States of Americaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
PNAS-2012-Zhang-13331-6.pdf
Size:
2.39 MB
Format:
Adobe Portable Document Format
Description:
Publisher's Version
License bundle
Now showing 1 - 1 of 1
Name:
VTUL_Distribution_License_2016_05_09.pdf
Size:
18.09 KB
Format:
Adobe Portable Document Format
Description: