title: Host cell factor-1 recruitment to E2F-bound and cell-cycle-control genes is mediated by THAP11 and ZNF143.
abstract: Host cell factor-1 (HCF-1) is a metazoan transcriptional coregulator essential for cell-cycle progression and cell proliferation. Current models suggest a mechanism whereby HCF-1 functions as a direct coregulator of E2F proteins, facilitating the expression of genes necessary for cell proliferation. In this report, we show that HCF-1 recruitment to numerous E2F-bound promoters is mediated by the concerted action of zinc finger transcription factors THAP11 and ZNF143, rather than E2F proteins directly. THAP11, ZNF143, and HCF-1 form a mutually dependent complex on chromatin, which is independent of E2F occupancy. Disruption of the THAP11/ZNF143/HCF-1 complex results in altered expression of cell-cycle control genes and leads to reduced cell proliferation, cell-cycle progression, and cell viability. These data establish a model in which a THAP11/ZNF143/HCF-1 complex is a critical component of the transcriptional regulatory network governing cell proliferation.
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: J Brandon
authors.initials: JB
authors.lastname: Parker
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Driskill Graduate Program in Life Sciences, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Yin
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Driskill Graduate Program in Life Sciences, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Aurimas
authors.initials: A
authors.lastname: Vinckevicius
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: debu@northwestern.edu.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chakravarti
mesh_terms: D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D035001:Host Factor 1 Protein / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D002843:Chromatin; D050684:E2F Transcription Factors; D035001:Host Factor 1 Protein; D046912:Multiprotein Complexes; D012097:Repressor Proteins; C498470:THAP11 protein, human; D015534:Trans-Activators; C114253:ZNF143 protein, human