title: The yeast cap binding complex modulates transcription factor recruitment and establishes proper histone H3K36 trimethylation during active transcription.
abstract: Recent studies have revealed a close relationship between transcription, histone modification, and RNA processing. In fact, genome-wide analyses that correlate histone marks with RNA processing signals raise the possibility that specific RNA processing factors may modulate transcription and help to "write" chromatin marks. Here we show that the nuclear cap binding complex (CBC) directs recruitment of transcription elongation factors and establishes proper histone marks during active transcription. A directed genetic screen revealed that deletion of either subunit of the CBC confers a synthetic growth defect when combined with deletion of genes encoding either Ctk2 or Bur2, a component of the Saccharomyces cerevisiae ortholog of P-TEFb. The CBC physically associates with these complexes to recruit them during transcription and mediates phosphorylation at Ser-2 of the C-terminal domain (CTD) of RNA polymerase II. To understand how these interactions influence downstream events, histone H3K36me3 was examined, and we demonstrate that CBCΔ affects proper Set2-dependent H3K36me3. Consistent with this, the CBC and Set2 have similar effects on the ability to rapidly induce and sustain activated gene expression, and these effects are distinct from other histone methyltransferases. This work provides evidence for an emerging model that RNA processing factors can modulate the recruitment of transcription factors and influence histone modification during elongation.
authors.affiliation: University of California, San Diego, Division of Biological Sciences, Molecular Biology Section, La Jolla, California, USA.
authors.forename: Munshi Azad
authors.initials: MA
authors.lastname: Hossain
authors.forename: Christina
authors.initials: C
authors.lastname: Chung
authors.forename: Suman K
authors.initials: SK
authors.lastname: Pradhan
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Johnson
mesh_terms: D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005686:Galactokinase / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: C414164:Bur2 protein, S cerevisiae; C118305:CTDK-I protein complex, S cerevisiae; D016213:Cyclins; D006657:Histones; D039502:Nuclear Cap-Binding Protein Complex; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D011494:Protein Kinases; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase; D012319:RNA Polymerase II