Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells.
Human HCF-1 is a large, highly conserved, and abundant nuclear protein that plays an important but unknown role in cell proliferation. It also plays a role in activation of herpes simplex virus immediate-early gene transcription by the viral regulatory protein VP16. A single proline-to-serine substitution in the HCF-1 VP16 interaction domain causes a temperature-induced arrest of cell proliferation in hamster tsBN67 cells and prevents transcriptional activation by VP16. We show here that HCF-1 is naturally bound to chromatin in uninfected cells through its VP16 interaction domain. HCF-1 is chromatin bound in tsBN67 cells at permissive temperature but dissociates from chromatin before tsBN67 cells stop proliferating at the nonpermissive temperature, suggesting that loss of HCF-1 chromatin association is the primary cause of the temperature-induced tsBN67 cell proliferation arrest. We propose that the role of HCF-1 in cell proliferation is to regulate gene transcription by associating with a multiplicity of DNA-bound transcription factors through its VP16 interaction domain.
Wysocka
J
J
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Reilly
P T
PT
Herr
W
W
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D006224:Cricetinae; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013696:Temperature; D014157:Transcription Factors
D002843:Chromatin; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors