Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells

作者：Joanna Wysocka, Patrick T. Reilly, Winship Herr · 发表于：Molecular and Cellular Biology · 年份：2001 · DOI：10.1128/mcb.21.11.3820-3829.2001 · 被引用次数：202 · 研究领域：interferon and immune responses、Virus-based gene therapy research、NF-κB Signaling Pathways

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.