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PMID: 16227571 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 25 ·No. 21 ·2005-11-00 ·Pages 9175-88

Smith ER, Cayrou C, Huang R, Lane WS, Côté J, Lucchesi JC

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 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 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.

MeSH Terms
Acetylation Alternative Splicing Amino Acid Sequence Animals Cell Cycle Chromatin/metabolism Chromosomal Proteins, Non-Histone DNA-Binding Proteins/genetics Drosophila Proteins/genetics Histone Acetyltransferases/genetics,metabolism Histones/metabolism Host Factor 1 Protein/metabolism Humans Lysine/metabolism Molecular Sequence Data Nuclear Proteins/genetics Protein Binding Sequence Homology, Amino Acid Transcription Factors/genetics,metabolism
Chemicals
Chromatin Chromosomal Proteins, Non-Histone DNA-Binding Proteins Drosophila Proteins Histones Host Factor 1 Protein MSL3 protein, human Nuclear Proteins Transcription Factors msl-1 protein, Drosophila msl-2 protein, Drosophila msl-3 protein, Drosophila Histone Acetyltransferases KAT8 protein, human mof protein, Drosophila Lysine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Smith Edwin R
Department of Biology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USA.
Cayrou Christelle
Huang Rong
Lane William S
Côté Jacques
Lucchesi John C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.21.9175-9188.2005
Published
2005-11-00
Pages
9175-88
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1265810
Subset
IM
Grants
Canadian Institutes of Health Research · 64289-1 · Canada
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1128/MCB.25.21.9175-9188.2005 PMC Full Text View journal details
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