This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Denis, H.
Right arrow Articles by Fuks, F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Denis, H.
Right arrow Articles by Fuks, F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2009, p. 4982-4993, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00285-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Connection between Deimination and Deacetylation of Histones{triangledown}

Hélène Denis,1 Rachel Deplus,1 Pascale Putmans,1 Michiyuki Yamada,2 Raphaël Métivier,3 and François Fuks1*

Free University of Brussels, Faculty of Medicine, Laboratory of Cancer Epigenetics, 808 route de Lennik, 1070 Brussels, Belgium,1 Graduate School of Integrated Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan,2 Equipe SPARTE, UMR CNRS 6026, Université de Rennes I, Campus de Beaulieu, 35042 Rennes Cedex, France3

Received 4 March 2009/ Returned for modification 28 March 2009/ Accepted 29 June 2009

Histone methylation plays key roles in regulating chromatin structure and function. The recent identification of enzymes that antagonize or remove histone methylation offers new opportunities to appreciate histone methylation plasticity in the regulation of epigenetic pathways. Peptidylarginine deiminase 4 (PADI4; also known as PAD4) was the first enzyme shown to antagonize histone methylation. PADI4 functions as a histone deiminase converting a methylarginine residue to citrulline at specific sites on the tails of histones H3 and H4. This activity is linked to repression of the estrogen-regulated pS2 promoter. Very little is known as to how PADI4 silences gene expression. We show here that PADI4 associates with the histone deacetylase 1 (HDAC1). Kinetic chromatin immunoprecipitation assays revealed that PADI4 and HDAC1, and the corresponding activities, associate cyclically and coordinately with the pS2 promoter during repression phases. Knockdown of HDAC1 led to decreased H3 citrullination, concomitantly with increased histone arginine methylation. In cells with a reduced HDAC1 and a slightly decreased PADI4 level, these effects were more pronounced. Our data thus suggest that PADI4 and HDAC1 collaborate to generate a repressive chromatin environment on the pS2 promoter. These findings further substantiate the "transcriptional clock" concept, highlighting the dynamic connection between deimination and deacetylation of histones.

* Corresponding author. Mailing address: Free University of Brussels, Faculty of Medicine, Laboratory of Cancer Epigenetics, 808 route de Lennik, 1070 Brussels, Belgium. Phone: 32-2-555-62-45. Fax: 32-2-555-62-57. E-mail: ffuks{at}ulb.ac.be

{triangledown} Published ahead of print on 6 July 2009.

Molecular and Cellular Biology, September 2009, p. 4982-4993, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00285-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»