title: Mitotic Activation of a Novel Histone Deacetylase 3-Linker Histone H1.3 Protein Complex by Protein Kinase CK2.
abstract: Histone deacetylase 3 (HDAC3) and linker histone H1 are involved in both chromatin compaction and the regulation of mitotic progression. However, the mechanisms by which HDAC3 and H1 regulate mitosis and the factors controlling HDAC3 and H1 activity during mitosis are unclear. Furthermore, as of now, no association between class I, II, or IV (non-sirtuin) HDACs and linker histones has been reported. Here we describe a novel HDAC3-H1.3 complex containing silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and nuclear receptor corepressor 1 (N-CoR) that accumulated in synchronized HeLa cells in late G2 phase and mitosis. Nonetheless, the deacetylation activity by HDAC3 in the complex was evident only in mitotic complexes. HDAC3 associated with H1.3 was highly phosphorylated on Ser-424 only during mitosis. Isolation of inactive HDAC3-H1.3 complexes from late G2 phase cells, and phosphorylation of HDAC3 in the complexes at serine 424 by protein kinase CK2 (also known as casein kinase 2) activated the HDAC3 in vitro. In vivo, CK2α and CK2α' double knockdown cells demonstrated a significant decrease in HDAC3 Ser-424 phosphorylation during mitosis. HDAC3 and H1.3 co-localized in between the chromosomes, with polar microtubules and spindle poles during metaphase through telophase, and partially co-localized with chromatin during prophase and interphase. H1 has been reported previously to associate with microtubules and, therefore, could potentially function in targeting HDAC3 to the microtubules. We suggest that phosphorylation of HDAC3 in the complex by CK2 during mitosis activates the complex for a dual role: compaction of the mitotic chromatin and regulation of polar microtubules dynamic instability.
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors.forename: Hemangi
authors.initials: H
authors.lastname: Patil
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors.forename: Carrie
authors.initials: C
authors.lastname: Wilks
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors.forename: Rhiannon W
authors.initials: RW
authors.lastname: Gonzalez
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Dhanireddy
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors.forename: Heather
authors.initials: H
authors.lastname: Conrad-Webb
authors.affiliation: From the Department of Biology, Texas Woman's University, Denton, Texas 76204 MBergel@twu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Bergel
mesh_terms: D000107:Acetylation; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D016195:G2 Phase; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008938:Mitosis; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D047390:Casein Kinase II; D002843:Chromatin; D006655:Histone Deacetylases; D006657:Histones; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D020033:Protein Isoforms; D011994:Recombinant Proteins; D012694:Serine; D000099186:Histone Deacetylase 3; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C570325:CSNK2A1 protein, human
keywords: chromatin; histone deacetylase 3 (HDAC3); linker histone H1.3; mitosis; mitotic spindle; protein kinase; protein kinase CK2