title: The C2H2-ZF transcription factor Zfp335 recognizes two consensus motifs using separate zinc finger arrays.
abstract: The complexities of DNA recognition by transcription factors (TFs) with multiple Cys2-His2 zinc fingers (C2H2-ZFs) remain poorly studied. We previously reported a mutation (R1092W) in the C2H2-ZF TF Zfp335 that led to selective loss of binding at a subset of targets, although the basis for this effect was unclear. We show that Zfp335 binds DNA and drives transcription via recognition of two distinct consensus motifs by separate ZF clusters and identify the specific motif interaction disrupted by R1092W. Our work presents Zfp335 as a model for understanding how C2H2-ZF TFs may use multiple recognition motifs to control gene expression.
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA; Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA;
authors.forename: Brenda Yuyuan
authors.identifier: 0000-0002-3212-875X
authors.initials: BY
authors.lastname: Han
authors.affiliation: Department of Computer Science, Stanford University, Stanford, California 94305, USA.
authors.forename: Chuan-Sheng
authors.initials: CS
authors.lastname: Foo
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA; Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA;
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA; Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA;
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C466083:ZNF335 protein, human; C000598773:zinc finger protein 335, mouse
keywords: ZNF335; Zfp335; protein–DNA binding; transcription factors; zinc fingers