The C2H2-ZF transcription factor Zfp335 recognizes two consensus motifs using separate zinc finger arrays

The complexities of DNA recognition by transcription factors with multiple Cys2-His2 zinc fingers (C2H2-ZFs) remain poorly studied. We previously reported a mutation (R1092W) in the C2H2-ZF transcription factor Zfp335 which led to selective loss of binding at a subset of targets, although the basis for this 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 utilize multiple recognition motifs to control gene expression. 3 ChIP-seq samples, 3 input samples from control Jurkat T cells or Jurkat cell lines overexpressing FLAG-tagged WT or bloto (R1092W) ZNF335