A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

SUMMARY The trace element zinc is required for proper functioning of a large number of proteins, including various enzymes. However, most zinc-containing proteins are transcription factors capable of binding DNA and are named zinc finger proteins. They form one of the largest families of transcriptional regulators and are categorized into various classes according to zinc-binding motifs. This review focuses on one class of zinc finger proteins called zinc cluster (or binuclear) proteins. Members of this family are exclusively fungal and possess the well-conserved motif CysX2CysX6CysX5-12CysX2CysX6-8Cys. The cysteine residues bind to two zinc atoms, which coordinate folding of the domain involved in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a transcriptional activator of genes involved in the catabolism of galactose in the budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other zinc cluster proteins have been characterized; they function in a wide range of processes, including primary and secondary metabolism and meiosis. Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more apparent that they are important regulators of fungal physiology.

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The Zinc Finger-Associated SCAN Box Is a Conserved Oligomerization Domain

Molecular and Cellular Biology ◽

10.1128/mcb.19.12.8526 ◽

1999 ◽

Vol 19 (12) ◽

pp. 8526-8535 ◽

Cited By ~ 57

Author(s):

Amy J. Williams ◽

Stephen C. Blacklow ◽

Tucker Collins

Keyword(s):

Zinc Finger ◽

Transcriptional Regulators ◽

Zinc Finger Proteins ◽

Rich Region ◽

Amino Terminal ◽

Self Association ◽

And Function ◽

Scan Domain ◽

Oligomerization Domain

ABSTRACT A number of Cys2His2 zinc finger proteins contain a highly conserved amino-terminal motif termed the SCAN domain. This element is an 80-residue, leucine-rich region that contains three segments strongly predicted to be α-helices. In this report, we show that the SCAN motif functions as an oligomerization domain mediating self-association or association with other proteins bearing SCAN domains. These findings suggest that the SCAN domain plays an important role in the assembly and function of this newly defined subclass of transcriptional regulators.

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Transcriptional regulation of sphingolipid metabolism in budding yeast

10.1101/2021.11.05.467429 ◽

2021 ◽

Author(s):

Nao Komatsu ◽

Yuko Ishino ◽

Rina Shirai ◽

Ken-taro Sakata ◽

Motohiro Tani ◽

...

Keyword(s):

Budding Yeast ◽

Transcriptional Regulators ◽

Negative Regulator ◽

Sphingolipid Metabolism ◽

Yeast Saccharomyces Cerevisiae ◽

Major Pathway ◽

Additional Layer ◽

Metabolism Enzymes ◽

Wide Range ◽

Sphingolipid Biosynthesis

Global control for the synthesis of lipids constituting a bilayer of cell membranes is known to be with a small number of transcription factors called master transcriptional regulators, which target a wide range of genes encoding lipid metabolism enzymes and/or their regulators. Although master transcriptional regulators of glycerophospholipids and sterols have been identified in both yeast and mammals, this aspect of sphingolipid metabolism is not yet understood. In the present study, we identified the C2H2-type zinc finger transcription factor, Com2, as a master transcriptional regulator of sphingolipid metabolism in the budding yeast, Saccharomyces cerevisiae. The target of rapamycin complex 2 (TORC2)-activated protein kinase Ypk1 is known to regulate sphingolipid metabolism. Activated Ypk1 stimulates the activity of serine palmitoyl transferase (SPT), the first-step enzyme in sphingolipid biosynthesis, by phosphorylating and inhibiting Orm1/2, a negative regulator of SPT. This regulation of SPT activity is thought to be a major pathway in the regulation of sphingolipid metabolism. In the present study, we found that inhibition of sphingolipid synthesis upregulates the expression of Com2, which in turn leads to the concomitant expression of Ypk1. The upregulation of Ypk1 expression was found to be dependent on a putative Com2-binding site in the YPK1 promoter. Our results also suggested that Com2 senses intracellular sphingolipid levels through a pathway independent of TORC2-Ypk1-mediated sensing of sphingolipids. Our results revealed an additional layer of mechanistic regulation that allows cells to maintain appropriate levels of sphingolipid biosynthesis and to rapidly induce this process in response to environmental stresses.

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Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma

Biomarker Research ◽

10.1186/s40364-021-00345-1 ◽

2022 ◽

Vol 10 (1) ◽

Author(s):

Xinxin Li ◽

Mengzhen Han ◽

Hongwei Zhang ◽

Furong Liu ◽

Yonglong Pan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcription Factors ◽

Zinc Finger ◽

Zinc Finger Proteins ◽

Biological Functions ◽

Binding Motifs ◽

Zinc Finger Motifs ◽

Tumorigenesis And Progression ◽

Long Time ◽

Underlying Mechanisms

AbstractZinc finger proteins are transcription factors with the finger domain, which plays a significant role in gene regulation. As the largest family of transcription factors in the human genome, zinc finger (ZNF) proteins are characterized by their different DNA binding motifs, such as C2H2 and Gag knuckle. Different kinds of zinc finger motifs exhibit a wide variety of biological functions. Zinc finger proteins have been reported in various diseases, especially in several cancers. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide, especially in China. Most of HCC patients have suffered from hepatitis B virus (HBV) and hepatitis C virus (HCV) injection for a long time. Although the surgical operation of HCC has been extremely developed, the prognosis of HCC is still very poor, and the underlying mechanisms in HCC tumorigenesis are still not completely understood. Here, we summarize multiple functions and recent research of zinc finger proteins in HCC tumorigenesis and progression. We also discuss the significance of zinc finger proteins in HCC diagnosis and prognostic evaluation.

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Faculty Opinions recommendation of Expanding the DNA-recognition repertoire for zinc finger proteins beyond 20 amino acids.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013240.189751 ◽

2003 ◽

Author(s):

Jennifer Cha

Keyword(s):

Amino Acids ◽

Zinc Finger ◽

Dna Recognition ◽

Zinc Finger Proteins

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Faculty Opinions recommendation of Reduction in DNA-binding affinity of Cys2His2 zinc finger proteins by linker phosphorylation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1019055.215578 ◽

2004 ◽

Author(s):

Philip Dawson

Keyword(s):

Dna Binding ◽

Binding Affinity ◽

Zinc Finger ◽

Zinc Finger Proteins ◽

Dna Binding Affinity

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Faculty Opinions recommendation of A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1053788.506625 ◽

2006 ◽

Author(s):

Robert K Herman

Keyword(s):

Zinc Finger ◽

Zinc Finger Proteins ◽

C Elegans ◽

Specific Pairing

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Control of Winged Waterprimrose (Jussiaea decurrens) and Northern Jointvetch (Aeschynomene virginica) with Fungal Pathogens

Weed Science ◽

10.1017/s0043174500044477 ◽

1979 ◽

Vol 27 (5) ◽

pp. 497-501 ◽

Cited By ~ 46

Author(s):

C. D. Boyette ◽

G. E. Templeton ◽

R. J. Smith

Keyword(s):

Oryza Sativa ◽

Glycine Max ◽

Fungal Pathogens ◽

Liquid Culture ◽

Field Experiments ◽

Colletotrichum Gloeosporioides ◽

Pathogenic Fungus ◽

Field Tests ◽

Wide Range ◽

Growing Region

An indigenous, host-specific, pathogenic fungus that parasitizes winged waterprimrose [Jussiaea decurrens(Walt.) DC.] is endemic in the rice growing region of Arkansas. The fungus was isolated and identified asColletotrichum gloeosporioides(Penz.) Sacc. f.sp. jussiaeae(CGJ). It is highly specific for parasitism of winged waterprimrose and not parasitic on creeping waterprimrose (J. repensL. var.glabrescensKtze.), rice (Oryza sativaL.), soybeans [Glycine max(L.) Merr.], cotton (Gossypium hirsutumL.), or 4 other crops and 13 other weeds. The fungus was physiologically distinct from C.gloeosporioides(Penz.) Sacc. f. sp.aeschynomene(CGA), an endemic anthracnose pathogen of northern jointvetch[Aeschynomene virginica(L.) B.S.P.], as indicated by cross inoculations of both weeds. Culture in the laboratory and inoculation of winged waterprimrose in greenhouse, growth chamber and field experiments indicated that the pathogen was stable, specific, and virulent in a wide range of environments. The pathogen yielded large quantities of spores in liquid culture. It is suitable for control of winged waterprimrose. Winged waterprimrose and northern jointvetch were controlled in greenhouse and field tests by application of spore mixtures of CGJ and CGA at concentrations of 1 to 2 million spores/ml of each fungus in 94 L/ha of water; the fungi did not damage rice or nontarget crops.

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Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility

Diagnostics ◽

10.3390/diagnostics11020246 ◽

2021 ◽

Vol 11 (2) ◽

pp. 246

Author(s):

Bogdan Doroftei ◽

Ovidiu-Dumitru Ilie ◽

Maria Puiu ◽

Alin Ciobica ◽

Ciprian Ilea

Keyword(s):

Motor Activity ◽

Experimental Model ◽

Zinc Finger ◽

Biomedical Research ◽

Zinc Finger Nucleases ◽

Loss Of Function ◽

Transcription Activator ◽

Phenotypic Changes ◽

Wide Range ◽

Short Palindromic Repeat

Infertility is a highly debated topic today. It has been long hypothesized that infertility has an idiopathic cause, but recent studies demonstrated the existence of a genetic substrate. Fortunately, the methods of editing the human genome proven to be revolutionary. Following research conducted, we identified a total of 21 relevant studies; 14 were performed on mice, 5 on zebrafish and 2 on rats. We concluded that over forty-four genes in total are dispensable for fertility in both sexes without affecting host homeostasis. However, there are genes whose loss-of-function induces moderate to severe phenotypic changes in both sexes. There were situations in which the authors reported infertility, exhibited by the experimental model, or other pathologies such as cryptorchidism, cataracts, or reduced motor activity. Overall, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 are techniques that offer a wide range of possibilities for studying infertility, even to create mutant variants. It can be concluded that ZFNs, TALENs, and CRISPR/Cas9 are crucial tools in biomedical research.

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