title: Chromatin condensation and recruitment of PHD finger proteins to histone H3K4me3 are mutually exclusive.
abstract: Histone post-translational modifications, and specific combinations they create, mediate a wide range of nuclear events. However, the mechanistic bases for recognition of these combinations have not been elucidated. Here, we characterize crosstalk between H3T3 and H3T6 phosphorylation, occurring in mitosis, and H3K4me3, a mark associated with active transcription. We detail the molecular mechanisms by which H3T3ph/K4me3/T6ph switches mediate activities of H3K4me3-binding proteins, including those containing plant homeodomain (PHD) and double Tudor reader domains. Our results derived from nuclear magnetic resonance chemical shift perturbation analysis, orthogonal binding assays and cell fluorescence microscopy studies reveal a strong anti-correlation between histone H3T3/T6 phosphorylation and retention of PHD finger proteins in chromatin during mitosis. Together, our findings uncover the mechanistic rules of chromatin engagement for H3K4me3-specific readers during cell division.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jovylyn
authors.initials: J
authors.lastname: Gatchalian
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain.
authors.forename: Carmen Mora
authors.initials: CM
authors.lastname: Gallardo
authors.affiliation: Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Shinsky
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Ruben Rosas
authors.initials: RR
authors.lastname: Ospina
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain.
authors.forename: Andrea Mansilla
authors.initials: AM
authors.lastname: Liendo
authors.affiliation: Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krajewski
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Brianna J
authors.initials: BJ
authors.lastname: Klein
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Forest H
authors.initials: FH
authors.lastname: Andrews
authors.affiliation: Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain kvanwely@cnb.csic.es.
authors.forename: Karel H
authors.initials: KH
authors.lastname: M van Wely
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA tatiana.kutateladze@ucdenver.edu.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D002843:Chromatin / Q000235:genetics*; D006570:Heterochromatin / Q000235:genetics*; D042421:Histone Code / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics; D008745:Methylation; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D000071856:Tudor Domain / Q000235:genetics
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase