Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

A Read/Write Mechanism Connects p300 Bromodomain Function to H2A.Z Acetylation


Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active regulatory regions associated with gene expression. Although the Tip60 complex is proposed to acetylate H2A.Z, functional studies suggest additional enzymes are involved. Here, we show that p300 acetylates H2A.Z at multiple lysines. In contrast, we found that although Tip60 does not efficiently acetylate H2A.Z in vitro, genetic inhibition of Tip60 reduces H2A.Zac in cells. Importantly, we found that interaction between the p300-bromodomain and H4 acetylation (H4ac) enhances p300-driven H2A.Zac. Indeed, H2A.Zac and H4ac show high genomic overlap, especially at active promoters. We also reveal unique chromatin features and transcriptional states at enhancers correlating with co-occurrence or exclusivity of H4ac and H2A.Zac. We propose that differential H4 and H2A.Z acetylation signatures can also define the enhancer state. In conclusion, we show both Tip60 and p300 contribute to H2A.Zac and reveal molecular mechanisms of writer/reader crosstalk between H2A.Z and H4 acetylation through p300.

Type Journal
ISBN 2589-0042 (Electronic) 2589-0042 (Linking)
Authors Colino-Sanguino, Y.; Cornett, E. M.; Moulder, D.; Smith, G. C.; Hrit, J.; Cordeiro-Spinetti, E.; Vaughan, R. M.; Krajewski, K.; Rothbart, S. B.; Clark, S. J.; Valdes-Mora, F.
Responsible Garvan Author Prof Susan Clark
Publisher Name iScience
Published Date 2019-10-31
Published Volume 21
Published Pages 773-788
Status Always Electronic
DOI 10.1016/j.isci.2019.10.053
URL link to publisher's version