title: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
abstract: Posttranslational histone modifications participate in modulating the structure and function of chromatin. Promoters of transcribed genes are enriched with K4 trimethylation and hyperacetylation on the N-terminal tail of histone H3. Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to interact with H3K4me3, indicating a biochemical link between K4 methylation and hyperacetylation. By using a combination of mass spectrometry, biochemistry, and NMR, we detail the Yng1 PHD-H3K4me3 interaction and the importance of NuA3-dependent acetylation at K14. Furthermore, genome-wide ChIP-Chip analysis demonstrates colocalization of Yng1 and H3K4me3 in vivo. Disrupting the K4me3 binding of Yng1 altered K14ac and transcription at certain genes, thereby demonstrating direct in vivo evidence of sequential trimethyl binding, acetyltransferase activity, and gene regulation by NuA3. Our data support a general mechanism of transcriptional control through which histone acetylation upstream of gene activation is promoted partially through availability of H3K4me3, "read" by binding modules in select subunits.
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Taverna
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: Serge
authors.initials: S
authors.lastname: Ilin
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Rogers
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Tanny
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Heather
authors.initials: H
authors.lastname: Lavender
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Baker
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103.
authors.forename: John
authors.initials: J
authors.lastname: Boyle
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Blair
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103.
authors.forename: John D
authors.initials: JD
authors.lastname: Aitchison
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205. Electronic address: ajtackett@uams.edu.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University. Electronic address: alliscd@rockefeller.edu.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
mesh_terms: D047369:Chromatin Immunoprecipitation; D016681:Genome, Fungal / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D016366:Open Reading Frames / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C459900:Yng1 protein, S cerevisiae