RT Journal
A1 Schmitges, Frank W.
A1 Radovani, Ernest
A1 Najafabadi, Hamed S.
A1 Barazandeh, Marjan
A1 Campitelli, Laura F.
A1 Yin, Yimeng
A1 Jolma, Arttu
A1 Zhong, Guoqing
A1 Guo, Hongbo
A1 Kanagalingam, Tharsan
A1 Dai, Wei F.
A1 Taipale, Jussi
A1 Emili, Andrew
A1 Greenblatt, Jack F.
A1 Hughes, Timothy R.
T1 Multiparameter functional diversity of human C2H2 zinc finger proteins
JF Genome Research 
JO Genome Research 
YR 2016 
FD December 01 
VO 26 
IS 12 
SP 1742 
OP 1752 
DO 10.1101/gr.209643.116 
UL http://genome.cshlp.org/content/26/12/1742.abstract 
AB 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.