Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor alpha target gene activation.
Authors
Zhang, XuesenBolt, Michael
Guertin, Michael J.
Chen, Wei
Zhang, Sheng
Cherrington, Brian D.
Slade, Daniel J.
Dreyton, Christina J.
Subramanian, Venkataraman
Bicker, Kevin L.
Thompson, Paul R
Mancini, Michael A.
Lis, John T.
Coonrod, Scott A.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2012-08-14Keywords
AnimalsArginine
*Biocatalysis
Cell Line, Tumor
Chromatin
Citrulline
Estrogen Receptor alpha
Estrogens
Gene Expression Regulation, Neoplastic
Genome, Human
Histones
Humans
Hydrolases
Mice
Nucleotide Motifs
Promoter Regions, Genetic
Response Elements
Transcription, Genetic
*Transcriptional Activation
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
Cofactors for estrogen receptor alpha (ERalpha) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ERalpha-positive cells with 17beta-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 ERalpha 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 ERalpha after E2 stimulation and that inhibition of either PAD2 or ERalpha strongly suppresses E2-induced H3R26 citrullination and ERalpha recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ERalpha, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.Source
Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13331-6. doi: 10.1073/pnas.1203280109 Link to article on publisher's siteDOI
10.1073/pnas.1203280109Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50023Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.1203280109