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Molecular and Cellular Biology, May 2008, p. 3401-3409, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.00006-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transcription-Coupled Methylation of Histone H3 at Lysine 36 Regulates Dosage Compensation by Enhancing Recruitment of the MSL Complex in Drosophila melanogaster{triangledown}

Oliver Bell,1 Thomas Conrad,2,{dagger} Jop Kind,2,{dagger} Christiane Wirbelauer,1 Asifa Akhtar,2* and Dirk Schübeler1*

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland,1 European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany2

Received 3 January 2008/ Returned for modification 28 January 2008/ Accepted 10 March 2008

In Drosophila melanogaster, dosage compensation relies on the targeting of the male-specific lethal (MSL) complex to hundreds of sites along the male X chromosome. Transcription-coupled methylation of histone H3 lysine 36 is enriched toward the 3' end of active genes, similar to the MSL proteins. Here, we have studied the link between histone H3 methylation and MSL complex targeting using RNA interference and chromatin immunoprecipitation. We show that trimethylation of histone H3 at lysine 36 (H3K36me3) relies on the histone methyltransferase Hypb and is localized promoter distal at dosage-compensated genes, similar to active genes on autosomes. However, H3K36me3 has an X-specific function, as reduction specifically decreases acetylation of histone H4 lysine 16 on the male X chromosome. This hypoacetylation is caused by compromised MSL binding and results in a failure to increase expression twofold. Thus, H3K36me3 marks the body of all active genes yet is utilized in a chromosome-specific manner to enhance histone acetylation at sites of dosage compensation.


* Corresponding author. Mailing address for Asifa Akhtar: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Phone: 49 6221 387 550. Fax: 49 6221 387 518. E-mail: akhtar{at}embl.de. Mailing address for Dirk Schübeler: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. Phone: 41 61 697 8269. Fax: 41 61 697 3976. E-mail: dirk{at}fmi.ch

{triangledown} Published ahead of print on 17 March 2008.

{dagger} Equally contributing authors.


Molecular and Cellular Biology, May 2008, p. 3401-3409, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.00006-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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