A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16.
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.
Smith
Edwin R
ER
Department of Biology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USA.
Cayrou
Christelle
C
Huang
Rong
R
Lane
William S
WS
Côté
Jacques
J
Lucchesi
John C
JC
D000107:Acetylation; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D035001:Host Factor 1 Protein / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D035001:Host Factor 1 Protein; C120701:MSL3 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila; C093904:msl-3 protein, Drosophila; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C111063:mof protein, Drosophila; D008239:Lysine