title: Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility.
abstract: The Tudor domain of human PHF1 recognizes trimethylated lysine 36 of histone H3 (H3K36me3). This interaction modulates the methyltransferase activity of the PRC2 complex and has a role in retention of PHF1 at DNA damage sites. We have previously determined the structural basis for the association of Tudor with a methylated histone peptide. Here we detail the molecular mechanism of binding of the Tudor domain to the H3KC36me3-nucleosome core particle (H3KC36me3-NCP). Using a combination of TROSY NMR and FRET, we show that Tudor concomitantly interacts with H3K36me3 and DNA. Binding of the PHF1 Tudor domain to the H3KC36me3-NCP stabilizes the nucleosome in a conformation in which the nucleosomal DNA is more accessible to DNA-binding regulatory proteins. Our data provide a mechanistic explanation for the consequence of reading of the active mark H3K36me3 by the PHF1 Tudor domain.
authors.affiliation: 1] Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA [2].
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Musselman
authors.affiliation: Department of Physics, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Gibson
authors.affiliation: Program in Structural Biology and Biochemistry, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Hartwick
authors.affiliation: Department of Physics, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Jovylyn
authors.initials: J
authors.lastname: Gatchalian
authors.affiliation: Department of Physics, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
authors.affiliation: 1] Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA [2] Program in Structural Biology and Biochemistry, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; C112309:PHF1 protein, human; D010455:Peptides; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D004247:DNA; D008239:Lysine