An RNA-interference screen in Drosophila to identify ZAD-containing C2H2 zinc finger genes that function in female germ cells

Abstract The zinc finger-associated domain (ZAD) is present in over 90 C2H2 zinc finger (ZNF) proteins. Despite their abundance, only a few ZAD-ZNF genes have been characterized to date. Here, we systematically analyze the function of 68 ZAD-ZNF genes in Drosophila female germ cells by performing an in vivo RNA-interference screen. We identified eight ZAD-ZNF genes required for oogenesis, and based on further characterization of the knockdown phenotypes, we uncovered defects broadly consistent with functions in germ cell specification and/or survival, early differentiation, and egg chamber maturation. These results provide a candidate pool for future studies aimed at functionalization of this large but poorly characterized gene family.

Download Full-text

Genome-wide characterization of the C2H2 zinc-finger genes in Cucumis sativus and functional analyses of four CsZFPs in response to stresses

BMC Plant Biology ◽

10.1186/s12870-020-02575-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Junliang Yin ◽

Lixin Wang ◽

Jiao Zhao ◽

Yiting Li ◽

Rong Huang ◽

...

Keyword(s):

Cucumis Sativus ◽

Zinc Finger ◽

C2h2 Zinc Finger ◽

Genome Wide ◽

Zinc Finger Genes ◽

Functional Analyses

Download Full-text

A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates

Development ◽

10.1242/dev.126.6.1259 ◽

1999 ◽

Vol 126 (6) ◽

pp. 1259-1268 ◽

Cited By ~ 1

Author(s):

A. Meng ◽

B. Moore ◽

H. Tang ◽

B. Yuan ◽

S. Lin

Keyword(s):

Transcription Factor ◽

Zinc Finger ◽

Dna Binding Domain ◽

Related Gene ◽

Presomitic Mesoderm ◽

Zinc Finger Gene ◽

Human And Mouse

The Drosophila doublesex (dsx) gene encodes a transcription factor that mediates sex determination. We describe the characterization of a novel zebrafish zinc-finger gene, terra, which contains a DNA binding domain similar to that of the Drosophila dsx gene. However, unlike dsx, terra is transiently expressed in the presomitic mesoderm and newly formed somites. Expression of terra in presomitic mesoderm is restricted to cells that lack expression of MyoD. In vivo, terra expression is reduced by hedgehog but enhanced by BMP signals. Overexpression of terra induces rapid apoptosis both in vitro and in vivo, suggesting that a tight regulation of terra expression is required during embryogenesis. Terra has both human and mouse homologs and is specifically expressed in mouse somites. Taken together, our findings suggest that terra is a highly conserved protein that plays specific roles in early somitogenesis of vertebrates.

Download Full-text

Identification and effect of Zf-AD-containing C2H2 zinc finger genes on BmNPV replication in the silkworm (Bombyx mori)

Pesticide Biochemistry and Physiology ◽

10.1016/j.pestbp.2020.104678 ◽

2020 ◽

Vol 170 ◽

pp. 104678

Author(s):

Chunlin Li ◽

Hao Zhang ◽

Rui Gao ◽

Weidong Zuo ◽

Yanyu Liu ◽

...

Keyword(s):

Bombyx Mori ◽

Zinc Finger ◽

C2h2 Zinc Finger ◽

Zinc Finger Genes ◽

Silkworm Bombyx Mori

Download Full-text

A survey of well conserved families of C2H2 zinc-finger genes in Daphnia

BMC Genomics ◽

10.1186/1471-2164-11-276 ◽

2010 ◽

Vol 11 (1) ◽

pp. 276 ◽

Cited By ~ 19

Author(s):

Arun Seetharam ◽

Yang Bai ◽

Gary W Stuart

Keyword(s):

Zinc Finger ◽

C2h2 Zinc Finger ◽

Zinc Finger Genes

Download Full-text

Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni

eLife ◽

10.7554/elife.33221 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 21

Author(s):

George R Wendt ◽

Julie NR Collins ◽

Jimin Pei ◽

Mark S Pearson ◽

Hayley M Bennett ◽

...

Keyword(s):

Stem Cells ◽

Zinc Finger ◽

Broad Spectrum ◽

Transcriptional Regulators ◽

Vertebrate Species ◽

Outer Coat ◽

Free Living ◽

Cell Specification ◽

Tegumental Cell

Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification. These proteins are homologous to a protein essential for neoblast-driven epidermal maintenance in free-living flatworms. Therefore, we speculate that related parasites (i.e., tapeworms and flukes) employ similar strategies to control tegumental maintenance. Since parasitic flatworms infect every vertebrate species, understanding neoblast-driven tegumental maintenance could identify broad-spectrum therapeutics to fight diseases caused by these parasites.

Download Full-text

Evolution of C2H2-zinc finger genes revisited

BMC Evolutionary Biology ◽

10.1186/1471-2148-9-51 ◽

2009 ◽

Vol 9 (1) ◽

pp. 51 ◽

Cited By ~ 22

Author(s):

James H Thomas ◽

Ryan O Emerson

Keyword(s):

Zinc Finger ◽

C2h2 Zinc Finger ◽

Zinc Finger Genes

Download Full-text

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

Science ◽

10.1126/science.aat0572 ◽

2018 ◽

Vol 362 (6414) ◽

pp. eaat0572 ◽

Cited By ~ 87

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.

Download Full-text

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

Nucleic Acids Research ◽

10.1093/nar/gkaa384 ◽

2020 ◽

Vol 48 (11) ◽

pp. 5986-6000 ◽

Cited By ~ 1

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.

Download Full-text