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


RESULTS
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
These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation.
Lee
Soyoung
S
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
Horn
Virginie
V
Julien
Eric
E
Liu
Yi
Y
Wysocka
Joanna
J
Bowerman
Bruce
B
Hengartner
Michael O
MO
Herr
Winship
W
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D051863:Host Cell Factor C1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009154:Mutation; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C497692:HCFC1 protein, human; D006657:Histones; D051863:Host Cell Factor C1; C497691:hcf-1 protein, C elegans; D012694:Serine