The forkhead transcription factor FOXK2 acts as a chromatin targeting factor for the BAP1-containing histone deubiquitinase complex

Nucleic Acids Res. 2014 Jun;42(10):6232-42. doi: 10.1093/nar/gku274. Epub 2014 Apr 19.

Abstract

There are numerous forkhead transcription factors in mammalian cells but we know little about the molecular functions of the majority of these. FOXK2 is a ubiquitously expressed family member suggesting an important function across multiple cell types. Here, we show that FOXK2 binds to the SIN3A and PR-DUB complexes. The PR-DUB complex contains the important tumour suppressor protein, the deubiquitinase BAP1. FOXK2 recruits BAP1 to DNA, promotes local histone deubiquitination and causes changes in target gene activity. Our results therefore provide an important link between BAP1 and the transcription factor FOXK2 and demonstrate how BAP1 can be recruited to specific regulatory loci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromatin / enzymology
  • Chromatin / metabolism*
  • Forkhead Transcription Factors / chemistry
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation
  • Genome
  • Humans
  • Protein Interaction Domains and Motifs
  • Repressor Proteins / metabolism
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin Thiolesterase / chemistry
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • BAP1 protein, human
  • Chromatin
  • Forkhead Transcription Factors
  • Repressor Proteins
  • SIN3A transcription factor
  • Tumor Suppressor Proteins
  • interleukin binding factor
  • Ubiquitin Thiolesterase
  • Sin3 Histone Deacetylase and Corepressor Complex