Host cell factor-1 recruitment to E2F-bound and cell-cycle-control genes is mediated by THAP11 and ZNF143

Cell Rep. 2014 Nov 6;9(3):967-82. doi: 10.1016/j.celrep.2014.09.051. Epub 2014 Oct 30.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Cell Cycle Checkpoints / genetics*
  • Cell Proliferation
  • Chromatin / metabolism
  • E2F Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HeLa Cells
  • Host Factor 1 Protein / metabolism*
  • Humans
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Repressor Proteins / metabolism*
  • Trans-Activators / metabolism*


  • Chromatin
  • E2F Transcription Factors
  • Host Factor 1 Protein
  • Multiprotein Complexes
  • Repressor Proteins
  • THAP11 protein, human
  • Trans-Activators
  • ZNF143 protein, human