Functional interactions between NURF and Ctcf regulate gene expression

Mol Cell Biol. 2015 Jan;35(1):224-37. doi: 10.1128/MCB.00553-14. Epub 2014 Oct 27.

Abstract

Gene expression frequently requires chromatin-remodeling complexes, and it is assumed that these complexes have common gene targets across cell types. Contrary to this belief, we show by genome-wide expression profiling that Bptf, an essential and unique subunit of the nucleosome-remodeling factor (NURF), predominantly regulates the expression of a unique set of genes between diverse cell types. Coincident with its functions in gene expression, we observed that Bptf is also important for regulating nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. NURF function at Ctcf binding sites could be direct, because Bptf occupies Ctcf binding sites in vivo and has physical interactions with CTCF and the cohesin subunit SA2. Assays of several Ctcf binding sites using reporter assays showed that their regulatory activity requires Bptf in two different cell types. Focused studies at H2-K1 showed that Bptf regulates the ability of Klf4 to bind near an upstream Ctcf site, possibly influencing gene expression. In combination, these studies demonstrate that gene expression as regulated by NURF occurs partly through physical and functional interactions with the ubiquitous and multivalent factors Ctcf and cohesin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism*
  • Binding Sites
  • CCCTC-Binding Factor
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Embryonic Stem Cells / cytology*
  • Gene Expression Regulation
  • Histones / metabolism
  • Kruppel-Like Factor 4
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism*
  • Nucleosomes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • Repressor Proteins / metabolism*
  • Transcription Factors / metabolism*

Substances

  • Antigens, Nuclear
  • CCCTC-Binding Factor
  • Chromatin
  • Ctcf protein, mouse
  • Histones
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Nerve Tissue Proteins
  • Nucleosomes
  • Repressor Proteins
  • Transcription Factors
  • fetal Alzheimer antigen
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex