title: Protein kinase A-mediated serine 35 phosphorylation dissociates histone H1.4 from mitotic chromosome.
abstract: Global histone H1 phosphorylation correlates with cell cycle progression. However, the function of site-specific H1 variant phosphorylation remains unclear. Our mass spectrometry analysis revealed a novel N-terminal phosphorylation of the major H1 variant H1.4 at serine 35 (H1.4S35ph), which accumulates at mitosis immediately after H3 phosphorylation at serine 10. Protein kinase A (PKA) was found to be a kinase for H1.4S35. Importantly, Ser-35-phosphorylated H1.4 dissociates from mitotic chromatin. Moreover, H1.4S35A substitution mutant cannot efficiently rescue the mitotic defect following H1.4 depletion, and inhibition of PKA activity increases the mitotic chromatin compaction depending on H1.4. Our results not only indicate that PKA-mediated H1.4S35 phosphorylation dissociates H1.4 from mitotic chromatin but also suggest that this phosphorylation is necessary for specific mitotic functions.
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, Taipei 100, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chi-Shuen
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Department of Life Science, National Taiwan Ocean University, Keelung, Taiwan 20224; Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan 20224.
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Lo
authors.affiliation: Program of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, BP 10142-67404 Illkirch Cedex, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Scheer
authors.affiliation: Program of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, BP 10142-67404 Illkirch Cedex, France.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tora
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hang-Jen
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Medicine, National Taiwan University, Taipei 100, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. Electronic address: ljjuan@gate.sinica.edu.tw.
authors.forename: Li-Jung
authors.initials: LJ
authors.lastname: Juan
mesh_terms: D019943:Amino Acid Substitution; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D020125:Mutation, Missense; D010766:Phosphorylation / Q000502:physiology; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases