A zinc finger protein-encoding gene expressed in the post-meiotic phase of spermatogenesis

Denny, Paul; Ashworth, Alan

doi:10.1016/0378-1119(91)90202-m

Cited by 46 publications

(20 citation statements)

References 30 publications

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“…The LeR domain is rich in leucine and glutamic acid residues and contains alpha helices. The LeR is often found in KRAB-containing zinc finger proteins (2,7,10,24,35,36,51,55). The NT2 clone appears to be a homologue of a human cDNA clone, FPM315, previously identified by random cloning and sequencing (56).…”

Section: Resultsmentioning

confidence: 99%

“…1). The LeR domain is rich in leucine and highly conserved in a number of other zinc finger proteins (2,7,10,24,35,36,51,55). The LeR domain is sometimes found in zinc finger proteins containing KRAB; however, our deletion experiments suggest that this domain is not involved in the KRAB-mediated suppression of Col11a2 promoter by NT2 (Fig.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

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A Kruüppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the α2(XI) Collagen Gene

Tanaka

Tsumaki

Kozak

et al. 2002

Molecular and Cellular Biology

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Type XI collagen is composed of three chains, ␣1(XI), ␣2(XI), and ␣3(XI), and plays a critical role in the formation of cartilage collagen fibrils and in skeletal morphogenesis. It was previously reported that the ؊530-bp promoter segment of the ␣2(XI) collagen gene (Col11a2) was sufficient for cartilage-specific expression and that a 24-bp sequence from this segment was able to switch promoter activity from neural tissues to cartilage in transgenic mice when this sequence was placed in the heterologous neurofilament light gene (NFL) promoter. To identify a protein factor that bound to the 24-bp sequence of the Col11a2 promoter, we screened a mouse limb bud cDNA expression library in the yeast one-hybrid screening system and obtained the cDNA clone NT2. Sequence analysis revealed that NT2 is a zinc finger protein consisting of a Krüppel-associated box (KRAB) and is a homologue of human FPM315, which was previously isolated by random cloning and sequencing. The KRAB domain has been found in a number of zinc finger proteins and implicated as a transcriptional repression domain, although few target genes for KRAB-containing zinc finger proteins has been identified. Here, we demonstrate that NT2 functions as a negative regulator of Col11a2. In situ hybridization analysis of developing mouse cartilage showed that NT2 mRNA is highly expressed by hypertrophic chondrocytes but is minimally expressed by resting and proliferating chondrocytes, in an inverse correlation with the expression patterns of Col11a2. Gel shift assays showed that NT2 bound a specific sequence within the 24-bp site of the Col11a2 promoter. We found that Col11a2 promoter activity was inhibited by transfection of the NT2 expression vector in RSC cells, a chondrosarcoma cell line. The expression vector for mutant NT2 lacking the KRAB domain failed to inhibit Col11a2 promoter activity. These results demonstrate that KRABzinc finger protein NT2 inhibits transcription of its physiological target gene, suggesting a novel regulatory mechanism of cartilage-specific expression of Col11a2.Cartilage is a highly specialized tissue and serves as the template for the growth and development of most bones. Cartilage development is initiated by mesenchymal cell condensation, followed by a series of chondrocyte maturation processes including resting, proliferative, and hypertrophic stages. Cartilage contains an extensive extracellular matrix which includes type II, IX, and XI collagens and provides mechanical strength to resist compression in joints. Type II collagen, a major collagen in cartilage, forms collagen fibrils and provides a structural framework for cartilage matrix. Type XI collagen coassembles stoichiometrically with type II collagen in the fibrils, whereas the type IX collagen is associated with the surface of the fibrils (30,46).The type XI collagen molecule is composed of three subunits: ␣1(XI), ␣2(XI), and ␣3(XI) (32). The ␣3(XI) chain is a posttranslational variant of the ␣1(II) chain (14), whereas the ␣1(XI) and ␣2(XI) chains are distinct gene prod...

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Section: Resultsmentioning

confidence: 99%

Section: R E T R a C T E Dmentioning

confidence: 99%

A Kruüppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the α2(XI) Collagen Gene

Tanaka

Tsumaki

Kozak

et al. 2002

Molecular and Cellular Biology

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“…55365), a gene with unknown function, but some similarity to LR8 (23). The GenomeScan model gene Hs7_7861_26_7_2 exhibits similarity to mouse zinc finger protein 29 (27). The remaining eight genes all exhibit similarity to members of a family of GTPbinding proteins, the immune-associated nucleotides (Ian genes).…”

Section: Resultsmentioning

confidence: 99%

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Hornum¹,

Rømer

Markholst³

2002

Diabetes

152

143

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1Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling human type 1 diabetes. They also exhibit lifelong T-cell lymphopenia. Functional and genetic data support the hypothesis that the gene responsible for the lymphopenia, Lyp, is also a diabetes susceptibility gene, named Iddm1. We constructed a 550-kb P1-derived artificial chromosome contig of the region. Here, we present a corrected genetic map reducing the genetic interval to 0.2 cM and the physical interval to 150 -290 kb. A total of 13 genes and six GenomeScan models are assigned to the homologous human DNA segment on HSA7q36.1, 8 of which belong to the family of immune-associated nucleotides (Ian genes). Two of these are orthologous to mouse Ian1 and -4, both excellent candidates for Iddm1. In normal rats, they are expressed in the thymus and T-cell regions of the spleen. In the thymus of lymphopenic rats, Ian1 exhibits wild-type expression patterns, whereas Ian4 expression is reduced. Mutational screening of their coding sequences revealed a frameshift mutation in Ian4 among lymphopenic rats. The mutation results in a truncated protein in which the COOH-terminal 215 amino acids-including the anchor localizing the protein to the outer mitochondrial membrane-are replaced by 19 other amino acids. We propose that Ian4 is identical to Iddm1.

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“…Various approaches have been developed to identify specific genes encoding transcription factors and DNA-binding proteins in the testis (5,7,9,10,40). In these studies, the target genes have been identified by homologous hybridization screenings of cDNA and genomic libraries and by polymerase chain reaction amplification with degenerate primers encompassing conserved DNA-binding domains.…”

mentioning

confidence: 99%

A testis-specific gene encoding a nuclear high-mobility-group box protein located in elongating spermatids.

Boissonneault¹,

Lau²

1993

Mol. Cell. Biol.

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A cDNA encoding a DNA-binding protein has been isolated by screening a mouse testicular expression cDNA library with a concatemer of a 12-bp putative protein-binding element present in the promoter of the testis-specific gene PGK-2. Sequence analysis of the isolated cDNA indicated the presence of an open reading frame that encodes a protein with two conserved DNA-binding motifs known as the high-mobility-group (HMG) boxes. Northern (RNA) blot analysis demonstrated that expression of the gene is restricted to the postpuberal testis. The DNA-binding activity and sequence specificity of the recombinant HMG protein were confirmed by DNA mobility shift assay using the initial concatemer of the PGK-2 promoter element as a probe as well as the wild-type or mutated versions of the 12-bp element within its natural sequence context. Immunocytochemical staining of adult testis sections with polyclonal antisera recognizing this recombinant HMG protein demonstrated that it is located predominantly in the nuclei of elongated spermatids at steps 9 and 10. These results suggest that this novel HMG box protein gene may be involved in the regulation of gene expression of the haploid male genome. The gene from which the cDNA was derived has been termed testis-specific HMG (tsHMG).

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A zinc finger protein-encoding gene expressed in the post-meiotic phase of spermatogenesis

Cited by 46 publications

References 30 publications

A Kruüppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the α2(XI) Collagen Gene

A Kruüppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the α2(XI) Collagen Gene

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

A testis-specific gene encoding a nuclear high-mobility-group box protein located in elongating spermatids.

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