A WIZ/Cohesin/CTCF Complex Anchors DNA Loops to Define Gene Expression and Cell Identity

Cell Rep. 2020 Apr 14;31(2):107503. doi: 10.1016/j.celrep.2020.03.067.


Chromosome structure is a key regulator of gene expression. CTCF and cohesin play critical roles in structuring chromosomes by mediating physical interactions between distant genomic sites. The resulting DNA loops often contain genes and their cis-regulatory elements. Despite the importance of DNA loops in maintaining proper transcriptional regulation and cell identity, there is limited understanding of the molecular mechanisms that regulate their dynamics and function. We report a previously unrecognized role for WIZ (widely interspaced zinc finger-containing protein) in DNA loop architecture and regulation of gene expression. WIZ forms a complex with cohesin and CTCF that occupies enhancers, promoters, insulators, and anchors of DNA loops. Aberrant WIZ function alters cohesin occupancy and increases the number of DNA loop structures in the genome. WIZ is required for proper gene expression and transcriptional insulation. Our results uncover an unexpected role for WIZ in DNA loop architecture, transcriptional control, and maintenance of cell identity.

Keywords: CTCF; DNA loop; WIZ; cellular identity; cohesin; gene expression; genome organization; stem cell; transcription.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites / genetics
  • CCCTC-Binding Factor / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromatin
  • Chromatin Immunoprecipitation / methods
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes / metabolism
  • Cohesins
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics
  • Genome / genetics
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Promoter Regions, Genetic / genetics


  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • WIZ protein, human
  • Wiz protein, mouse
  • DNA