title: Multiparameter functional diversity of human C2H2 zinc finger proteins.
abstract: C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein-protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Schmitges
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Radovani
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Hamed S
authors.initials: HS
authors.lastname: Najafabadi
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Barazandeh
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Campitelli
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE 141 83, Sweden.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Biosciences and Nutrition, Karolinska Institutet, SE 141 83, Sweden.
authors.forename: Arttu
authors.initials: A
authors.lastname: Jolma
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Tharsan
authors.initials: T
authors.lastname: Kanagalingam
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Wei F
authors.initials: WF
authors.lastname: Dai
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE 141 83, Sweden.
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D001665:Binding Sites; D000070580:CYS2-HIS2 Zinc Fingers; D004247:DNA / Q000378:metabolism*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D060066:Protein Interaction Maps; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D004247:DNA