title: Diversification of transcription factor paralogs via noncanonical modularity in C2H2 zinc finger DNA binding.
abstract: A major challenge in obtaining a full molecular description of evolutionary adaptation is to characterize how transcription factor (TF) DNA-binding specificity can change. To identify mechanisms of TF diversification, we performed detailed comparisons of yeast C2H2 ZF proteins with identical canonical recognition residues that are expected to bind the same DNA sequences. Unexpectedly, we found that ZF proteins can adapt to recognize new binding sites in a modular fashion whereby binding to common core sites remains unaffected. We identified two distinct mechanisms, conserved across multiple Ascomycota species, by which this molecular adaptation occurred. Our results suggest a route for TF evolution that alleviates negative pleiotropic effects by modularly gaining new binding sites. These findings expand our current understanding of ZF DNA binding and provide evidence for paralogous ZFs utilizing alternate modes of DNA binding to recognize unique sets of noncanonical binding sites.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Biology, Boston University, Boston, MA 02215, USA. Electronic address: tsiggers@bu.edu.
authors.forename: Trevor
authors.initials: T
authors.lastname: Siggers
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Reddy
authors.affiliation: Department of Biology, Boston University, Boston, MA 02215, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Barron
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: mlbulyk@receptor.med.harvard.edu.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
mesh_terms: D020816:Amino Acid Motifs; D001203:Ascomycota / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004271:DNA, Fungal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D016681:Genome, Fungal; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D014157:Transcription Factors