Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells.

Authors: Lee S; Horn V; Julien E; Liu Y; Wysocka J; Bowerman B; Hengartner MO; Herr W

Abstract: BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation.

Keywords: Animals; Base Sequence; Caenorhabditis elegans/cytology/*metabolism; Caenorhabditis elegans Proteins/genetics/*metabolism; DNA Primers; *Epigenesis, Genetic; Histones/chemistry/*metabolism; Host Cell Factor C1/genetics/*metabolism; Humans; Microscopy, Fluorescence; Mutation; Phosphorylation; Serine/*metabolism
Journal: PloS one
Volume: 2
Issue: 11
Pages: e1213
Date: Nov. 29, 2007
PMID: 18043729
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Lee S, Horn V, Julien E, Liu Y, Wysocka J, Bowerman B, Hengartner MO, Herr W (2007) Epigenetic regulation of histone H3 serine 10 phosphorylation status by HCF-1 proteins in C. elegans and mammalian cells. PloS one 2: e1213.

Lifespan Factors:
  • HCFC1 host cell factor C1 (VP16-accessory protein)

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