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Molecular and Cellular Biology, June 2004, p. 5475-5484, Vol. 24, No. 12
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.12.5475-5484.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Differential Histone H3 Lys-9 and Lys-27 Methylation Profiles on the X Chromosome{dagger}

Claire Rougeulle,1* Julie Chaumeil,2 Kavitha Sarma,3 C. David Allis,4 Danny Reinberg,3 Philip Avner,1 and Edith Heard2*

Pasteur Institute, Paris 75015,1 Curie Institute, Paris 75005, France,2 Howard Hughes Medical Institute, Piscataway, New Jersey 08854,3 Rockefeller University, New York, New York 100214

Received 4 November 2003/ Returned for modification 9 December 2003/ Accepted 6 March 2004

Histone H3 tail modifications are among the earliest chromatin changes in the X-chromosome inactivation process. In this study we investigated the relative profiles of two important repressive marks on the X chromosome: methylation of H3 lysine 9 (K9) and 27 (K27). We found that both H3K9 dimethylation and K27 trimethylation characterize the inactive X in somatic cells and that their relative kinetics of enrichment on the X chromosome as it undergoes inactivation are similar. However, dynamic changes of H3K9 and H3K27 methylation on the inactivating X chromosome compared to the rest of the genome are distinct, suggesting that these two modifications play complementary and perhaps nonredundant roles in the establishment and/or maintenance of X inactivation. Furthermore, we show that a hotspot of H3K9 dimethylation 5' to Xist also displays high levels of H3 tri-meK27. However, analysis of this region in G9a mutant embryonic stem cells shows that these two methyl marks are dependent on different histone methyltransferases.

* Corresponding author. Mailing address for Claire Rougeulle: CNRS URA 2578, Unité de Génétique Moléculaire Murine, Institut Pasteur, 25 rue du Dr. Roux, Paris 75015, France. Phone: 33-1-45-68-86-53. Fax: 33-1-45-68-86-56. E-mail: rougeull{at}pasteur.fr. Mailing address for Edith Heard: CNRS UMR 218, Institut Curie, 26 rue d'Ulm, Paris 75005, France. Phone: 33-1-42-34-66-91. Fax: 33-1-46-33-30-16. E-mail: Edith.Heard{at}curie.fr.

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

Molecular and Cellular Biology, June 2004, p. 5475-5484, Vol. 24, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.12.5475-5484.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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