Direct binding of INHAT to H3 tails disrupted by modifications.
The N-terminal tails of histones are central to the regulation of chromatin structure. They form a binding platform for multiple protein complexes, which in turn regulate DNA processes such as transcription. Using peptide mass fingerprinting we identified INHAT (inhibitor of acetyltransferases) as a specific histone H3 N-terminal tail-binding complex. INHAT comprises two essential subunits, SET and pp32. We demonstrate that both SET and pp32 bind directly to the N terminus of H3. The binding is differentially affected by various modifications within the H3 N terminus. In particular, single phosphorylations within the H3 tail abrogates binding of INHAT, as does the simultaneous acetylation of multiple lysine residues. The histone modifications that affect INHAT binding are therefore compatible with its known role in transcriptional repression. We suggest that the charge of the histone tail is a major determinant in allowing INHAT to bind chromatin and coordinate the activity of multiple histone acetyltransferases.
Schneider
Robert
R
The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Bannister
Andrew J
AJ
Weise
Christoph
C
Kouzarides
Tony
T
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D008239:Lysine