CRISPR and biochemical screens identify MAZ as a cofactor in CTCF-mediated insulation at Hox clusters

Havva Ortabozkoyun, Pin Yao Huang, Hyunwoo Cho, Varun Narendra, Gary LeRoy, Edgar Gonzalez-Buendia, Jane A. Skok, Aristotelis Tsirigos, Esteban O. Mazzoni, Danny Reinberg

Research output: Contribution to journalArticlepeer-review


CCCTC-binding factor (CTCF) is critical to three-dimensional genome organization. Upon differentiation, CTCF insulates active and repressed genes within Hox gene clusters. We conducted a genome-wide CRISPR knockout (KO) screen to identify genes required for CTCF-boundary activity at the HoxA cluster, complemented by biochemical approaches. Among the candidates, we identified Myc-associated zinc-finger protein (MAZ) as a cofactor in CTCF insulation. MAZ colocalizes with CTCF at chromatin borders and, similar to CTCF, interacts with the cohesin subunit RAD21. MAZ KO disrupts gene expression and local contacts within topologically associating domains. Similar to CTCF motif deletions, MAZ motif deletions lead to derepression of posterior Hox genes immediately after CTCF boundaries upon differentiation, giving rise to homeotic transformations in mouse. Thus, MAZ is a factor contributing to appropriate insulation, gene expression and genomic architecture during development.

Original languageEnglish (US)
Pages (from-to)202-212
Number of pages11
JournalNature Genetics
Issue number2
StatePublished - Feb 2022


  • Animals
  • CCCTC-Binding Factor/chemistry
  • CRISPR-Cas Systems
  • Cell Cycle Proteins/metabolism
  • Cell Differentiation
  • Cell Line
  • Chromatin/metabolism
  • DNA-Binding Proteins/chemistry
  • Embryonic Stem Cells/cytology
  • Gene Editing
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins/genetics
  • Mice
  • Transcription Factors/chemistry

ASJC Scopus subject areas

  • Genetics


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