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CRISPR and biochemical screens identify MAZ as a cofactor in CTCF-mediated insulation at Hox clusters.
Ortabozkoyun, Havva; Huang, Pin-Yao; Cho, Hyunwoo; Narendra, Varun; LeRoy, Gary; Gonzalez-Buendia, Edgar; Skok, Jane A; Tsirigos, Aristotelis; Mazzoni, Esteban O; Reinberg, Danny.
Afiliação
  • Ortabozkoyun H; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY, USA.
  • Huang PY; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA.
  • Cho H; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY, USA.
  • Narendra V; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA.
  • LeRoy G; Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • Gonzalez-Buendia E; Applied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY, USA.
  • Skok JA; Department of Radiation Oncology, NYU Grossman School of Medicine, New York, NY, USA.
  • Tsirigos A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Mazzoni EO; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY, USA.
  • Reinberg D; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA.
Nat Genet ; 54(2): 202-212, 2022 02.
Article em En | MEDLINE | ID: mdl-35145304
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Genes Homeobox / Proteínas de Homeodomínio / Proteínas de Ligação a DNA / Células-Tronco Embrionárias / Fator de Ligação a CCCTC Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Genes Homeobox / Proteínas de Homeodomínio / Proteínas de Ligação a DNA / Células-Tronco Embrionárias / Fator de Ligação a CCCTC Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos