scholarly journals Characterization of Snail nuclear import pathways as representatives of C2H2 zinc finger transcription factors

2009 ◽  
Vol 122 (9) ◽  
pp. 1452-1460 ◽  
Author(s):  
J.-M. Mingot ◽  
S. Vega ◽  
B. Maestro ◽  
J. M. Sanz ◽  
M. A. Nieto
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Nuclear Import ◽  
C2h2 Zinc Finger

scholarly journals Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN

Science ◽  
2018 ◽  
Vol 362 (6414) ◽  
pp. eaat0572 ◽  
Author(s):  
Quinlan L. Sievers ◽  
Georg Petzold ◽  
Richard D. Bunker ◽  
Aline Renneville ◽  
Mikołaj Słabicki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Small Molecules ◽  
Zinc Finger ◽  
Ubiquitin Ligase ◽  
Biochemical Analysis ◽  
Zinc Fingers ◽  
Functional Characterization ◽  
C2h2 Zinc Finger

The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc finger domain to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase. We screened the human C2H2 zinc finger proteome for degradation in the presence of thalidomide analogs, identifying 11 zinc finger degrons. Structural and functional characterization of the C2H2 zinc finger degrons demonstrates how diverse zinc finger domains bind the permissive drug-CRBN interface. Computational zinc finger docking and biochemical analysis predict that more than 150 zinc fingers bind the drug-CRBN complex in vitro, and we show that selective zinc finger degradation can be achieved through compound modifications. Our results provide a rationale for therapeutically targeting transcription factors that were previously considered undruggable.

scholarly journals Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters

2020 ◽  
Vol 48 (11) ◽  
pp. 5986-6000 ◽  
Author(s):  
Weiya Ni ◽  
Andrew A Perez ◽  
Shannon Schreiner ◽  
Charles M Nicolet ◽  
Peggy J Farnham
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Cpg Island ◽  
Zinc Finger Proteins ◽  
Double Knockout ◽  
Altered Expression ◽  
C2h2 Zinc Finger ◽  
Necessary And Sufficient ◽  
Functional Analyses

Abstract Our study focuses on a family of ubiquitously expressed human C2H2 zinc finger proteins comprised of ZFX, ZFY and ZNF711. Although their protein structure suggests that ZFX, ZFY and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. We used CRISPR-mediated deletion to create bi-allelic knockouts of ZFX and/or ZNF711 in female HEK293T cells (which naturally lack ZFY). We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation. RNA-seq analysis revealed that thousands of genes showed altered expression in the double knockout clones, suggesting that these TFs are critical regulators of the transcriptome. To gain insight into how these TFs regulate transcription, we created mutant ZFX proteins and analyzed them for DNA binding and transactivation capability. We found that zinc fingers 11–13 are necessary and sufficient for DNA binding and, in combination with the N terminal region, constitute a functional transactivator. Our functional analyses of the ZFX family provides important new insights into transcriptional regulation in human cells by members of the large, but under-studied family of C2H2 zinc finger proteins.

Characterization of the isoforms of MOVO zinc finger protein, a mouse homologue of Drosophila Ovo, as transcription factors

Gene ◽  
2004 ◽  
Vol 336 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Sawako Unezaki ◽  
Mikio Nishizawa ◽  
Emiko Okuda-Ashitaka ◽  
Yasuo Masu ◽  
Masanori Mukai ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Protein A ◽  
Mouse Homologue ◽  
Finger Protein
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