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Molecular and Cellular Biology, March 2008, p. 1739-1754, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01180-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Histone H3 Tails Containing Dimethylated Lysine and Adjacent Phosphorylated Serine Modifications Adopt a Specific Conformation during Mitosis and Meiosis{triangledown} ,{dagger}

Adrien Eberlin,1 Cédric Grauffel,2,3,{ddagger} Mustapha Oulad-Abdelghani,1,{ddagger} Flavie Robert,1,{ddagger},§ Maria-Elena Torres-Padilla,1 Romain Lambrot,4 Danièle Spehner,2 Lourdes Ponce-Perez,1 Jean-Marie Würtz,2 Roland H. Stote,3 Sarah Kimmins,4 Patrick Schultz,2 Annick Dejaegere,2 and Laszlo Tora1*

Department of Transcription,1 Department of Structural Biology and Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, UMR7104, INSERM, U596, Université Louis Pasteur, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France,2 Laboratoire de Biophysicochimie Moléculaire, Institut de Chimie CNRS-ULP LC3-UMR7177, Université Louis Pasteur, Strasbourg, France,3 Departments of Animal Science and Pharmacology and Therapeutics, McGill University, Montreal, Canada4

Received 3 July 2007/ Returned for modification 11 October 2007/ Accepted 12 December 2007

Condensation of chromatin, mediated in part by posttranslational modifications of histones, is essential for cell division during mitosis. Histone H3 tails are dimethylated on lysine (Kme2) and become phosphorylated on serine (Sp) residues during mitosis. We have explored the possibility that these double modifications are involved in the establishment of H3 tail conformations during the cell cycle. Here we describe a specific chromatin conformation occurring at Kme2 and adjacently phosphorylated S of H3 tails upon formation of a hydrogen bond. This conformation appears exclusively between early prophase and early anaphase of the mitosis, when chromatin condensation is highest. Moreover, we observed that the conformed H3Kme2Sp tail is present at the diplotene and metaphase stages in spermatocytes and oocytes. Our data together with results obtained by cryoelectron microscopy suggest that the conformation of Kme2Sp-modified H3 tails changes during mitosis and meiosis. This is supported by biostructural modeling of a modified histone H3 tail bound by an antibody, indicating that Kme2Sp-modified H3 tails can adopt at least two different conformations. Thus, the H3K9me2S10p and the H3K27me2S28p sites are involved in the acquisition of specific chromatin conformations during chromatin condensation for cell division.


* Corresponding author. Mailing address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U.596, CNRS-LGME, ULP, Parc d'Innovation, 1, rue Laurent Fries, BP 10142, Illkirch Cedex, CU de Strasbourg 67404, France. Phone: 33 388 65 34 44. Fax: 33 388 65 32 01. E-mail: laszlo{at}igbmc.u-strasbg.fr

{triangledown} Published ahead of print on 7 January 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

§ Present address: Merck Serono Biotech Center, 1809 Corsier, Switzerland.


Molecular and Cellular Biology, March 2008, p. 1739-1754, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01180-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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