A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16

• Type of Material: Article
• Authors: Edwin Smith, Emory University; Christelle Cayrou, Laval University Cancer Research Center; Rong Huang, Emory University; William S. Lane, Harvard University; Jacques Cote, Laval University Cancer Research Center; John C. Lucchesi, Emory University
• Language: English
• Date: 2005-11-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2005, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/MCB.25.21.9175-9188.2005
• Title of Journal or Parent Work: Molecular and Cellular Biology
• ISSN: 0270-7306
• Volume: 25
• Issue: 21
• Start Page: 9175
• End Page: 9188
• Grant/Funding Information: Research support was provided by grants from the National Institutes of Health and the A. G. Candler Endowment to J.C.L. and from GenomeCanada/GenomeQuebec and the Canadian Institutes of Health Research (CIHR) to J.C.
• Keywords: Life Sciences & Biomedicine; ACETYLTRANSFERASE COMPLEX; Biochemistry & Molecular Biology; MALE X-CHROMOSOME; DOSAGE COMPENSATION COMPLEX; TRANSCRIPTIONAL REPRESSION; BIOCHEMISTRY & MOLECULAR BIOLOGY; GENE-EXPRESSION; MYST FAMILY; Science & Technology; RING FINGER; CELL BIOLOGY; CHROMATIN-STRUCTURE; H4 ACETYLATION; FUNCTIONAL-INTEGRATION; Cell Biology
• Research Categories: Biology, Microbiology; Health Sciences, Oncology; Biology, General

Abstract

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 MSU (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the pres ence 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 G 2 /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.