Mitotic activation of a novel histone deacetylase 3-linker histone H1.3 protein complex by protein kinase CK2
Wold Gonzalez, Rhiannon
MetadataShow full item record
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 as well as 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 SMRT and N-CoR which accumulated in synchronized HeLa cells in late G2 and mitosis. Nonetheless, the deacetylation activity by the HDAC3 in the complex was evident only in mitotic complexes. HDAC3 associated to H1.3 was highly phosphorylated on S424 only during mitosis. Isolation of inactive HDAC3-H1.3 complexes from late-G2 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 S424 phosphorylation during mitosis. HDAC3 and H1.3 colocalized in between the chromosomes, with polar microtubules and spindle poles during metaphase through telophase, and partially colocalized with chromatin during prophase and interphase. H1 was previously reported to associate with microtubules; thus 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 as well as regulation of the polar microtubules dynamic instability during mitosis. *This article was published with the assistance of the Texas Woman's University Libraries Open Access Fund. The original article can be found at: http://www.jbc.org/content/early/2015/12/09/jbc.M115.643874
Showing items related by title, author, creator and subject.
Gonzalez, Rhiannon (Texas Woman's University, 2016-05-30)The compaction level of chromatin regulates DNA accessibility, gene expression, and cell division. Transcription factors and other proteins cannot access the DNA within compacted chromatin. Two types of proteins that ...
Patil, Hemangi (2009-12)Eukaryotic DNA is organized with nucleoproteins into a dynamic structure named chromatin. Chromatin compaction and decompaction plays an important role in modulation of various DNA-dependent functions in the cell. Histone ...