TY  - JOUR
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
Y1  - 2016/12/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1742 
EP  - 1752 
DO  - 10.1101/gr.209643.116 
VL  - 26 
IS  - 12 
UR  - http://genome.cshlp.org/content/26/12/1742.abstract 
N2  - 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. 
ER  -