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Molecular and Cellular Biology, November 2005, p. 9175-9188, Vol. 25, No. 21
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.21.9175-9188.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16
Edwin R. Smith,1,2
Christelle Cayrou,3
Rong Huang,1
William S. Lane,4
Jacques Côté,3 and
John C. Lucchesi1*
Department of Biology,1
Department of Cell Biology, Emory University, Atlanta, Georgia 30322,2
Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Quebec City, Quebec G1R 2J6, Canada,3
Harvard Microchemistry Facility, Harvard University, Cambridge, Massachusetts 021384
Received 23 April 2005/
Returned for modification 20 May 2005/
Accepted 26 July 2005
We describe a stable, multisubunit human histone acetyltransferase complex (hMSL) that contains homologs of the Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3. This complex shows strong specificity for histone H4 lysine 16 in chromatin in vitro, and RNA interference-mediated knockdown experiments reveal that it is responsible for the majority of H4 acetylation at lysine 16 in the cell. We also find that hMOF is a component of additional complexes, forming associations with host cell factor 1 and a protein distantly related to MSL1 (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the presence of the chromodomain. Lastly, we find that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G2/M cell cycle arrest. This is of particular interest given the recent correlation of global loss of acetylation of lysine 16 in histone H4 with tumorigenesis.
* Corresponding author. Mailing address: Department of Biology, Emory University, 1510 Clifton Rd. NE, Atlanta, GA 30322. Phone: (404) 727-4234. Fax: (404) 727-2880. E-mail:
lucchesi{at}biology.emory.edu.
Molecular and Cellular Biology, November 2005, p. 9175-9188, Vol. 25, No. 21
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.21.9175-9188.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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