NuA4 links methylation of histone H3 lysines 4 and 36 to acetylation of histones H4 and H3

Daniel S. Ginsburg, Timi Elvuchio Anlembom, Jianing Wang, Sanket R. Patel, Bing Li, Alan G. Hinnebusch

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Cotranscriptional methylation of histone H3 lysines 4 and 36 by Set1 and Set2, respectively, stimulates interaction between nucleosomes and histone deacetylase complexes to block cryptic transcription in budding yeast. We previously showed that loss of all H3K4 and H3K36 methylation in a set1Δset2Δ mutant reduces interaction between native nucleosomes and the NuA4 lysine acetyltransferase (KAT) complex. We now provide evidence that NuA4 preferentially binds H3 tails mono- and dimethylated on H3K4 and di- and trimethylated on H3K36, an H3 methylation pattern distinct from that recognized by the RPD3C(S) and Hos2/Set3 histone deacetylase complexes (HDACs). Loss of H3K4 or H3K36 methylation in set1Δ or set2Δ mutants reduces NuA4 interaction with bulk nucleosomes in vitro and in vivo, and reduces NuA4 occupancy of transcribed coding sequences at particular genes. We also provide evidence that NuA4 acetylation of lysine residues in the histone H4 tail stimulates SAGA interaction with nucleosomes and its recruitment to coding sequences and attendant acetylation of histone H3 in vivo. Thus, H3 methylation exerts opposing effects of enhancing nucleosome acetylation by both NuA4 and SAGA as well as stimulating nucleosome deacetylation by multiple HDACs to maintain the proper level of histone acetylation in transcribed coding sequences.

Original languageEnglish (US)
Pages (from-to)32656-32670
Number of pages15
JournalJournal of Biological Chemistry
Issue number47
StatePublished - Nov 21 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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