Molecular cloning and characterization of a KRAB-containing zinc finger protein, ZNF317, and its isoforms.

To identify zinc finger genes in human primary cultured erythroid progenitor cells, RT-PCR was performed using primers specific for the conserved sequence in zinc finger domains of mouse Friend of GATA-1. We identified a novel Krüppel-associated box (KRAB) zinc finger gene, ZNF317. Evaluation of full-length cDNA obtained by RACE showed that it encoded a protein composed of 13 Krüppel-like zinc fingers and a KRAB domain. RT-PCR analysis revealed four alternatively splicing products (ZNF317-1 through ZNF317-4). The ZNF317 gene has seven exons and is located in human chromosome 19p13. Northern analysis revealed that ZNF317-1 and ZNF317-2 transcripts were ubiquitously expressed, whereas ZNF317-3 and ZNF317-4 transcripts were detected only in lymphocytes, spleen, and lung. Competitive RT-PCR analysis showed that the expression of ZNF317 mRNA significantly decreased during erythroid maturation. In lymphocytes, ZNF317 expression was reduced in response to mitogenic stimulation. We propose that ZNF317 may play an important role in erythroid maturation and lymphoid proliferation.

Takashima H ，Nishio H ，Wakao H ，Nishio M ，Koizumi K ，Oda A ，Koike T ，Sawada K ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Identification and characterization of human ZNF274 cDNA, which encodes a novel kruppel-type zinc-finger protein having nucleolar targeting ability.

A human cDNA encoding a novel zinc-finger protein, ZNF274, was identified by the "nuclear transportation trap" method (Ueki, N., Oda, T., Kondo, M., Yano, K., Noguchi, T., and Muramatsu, M., 1998, Nat. Biotechnol. 16: 1338-1342). Based on sequence analysis of the full-length cDNA, this novel gene has two alternative splicing forms, ZNF274a and ZNF274b, which encode putative proteins of 621 and 584 amino acids, respectively. ZNF274a contains five C2H2-type zinc-finger motifs, two KRAB-A (Kruppel-associated box) domains, and one leucine-rich domain. ZNF274b lacks the first KRAB-A domain at the N-terminus. ZNF274 mRNA is detected in various human tissues by Northern analysis. The ZNF274 gene is mapped distal to marker RP S28 1 in the human chromosome 19qter region, by RH mapping. The KRAB domains of ZNF274 exhibited transcription repressor activity when tested in GAL4 fusion protein assays. EGFP-ZNF274 fusion protein expressed in COS7 cells predominantly localized to the nucleoli. A series of deletion constructs revealed that a minimal domain consisting of the third and fourth zinc-fingers possesses nucleolar targeting ability. These results suggest that ZNF274 is a ubiquitous transcription repressor that plays a role in the nucleoli.

Yano K ，Ueki N ，Oda T ，Seki N ，Masuho Y ，Muramatsu M ... -  《GENOMICS》

Cloning and characterization of ZNF236, a glucose-regulated Kruppel-like zinc-finger gene mapping to human chromosome 18q22-q23.

We report the cDNA cloning and characterization of ZNF236, a novel Kruppel-like zinc-finger gene initially identified by its glucose-regulated expression in human mesangial cells using mRNA differential display. Using the differential display fragment as a probe, we screened a human fetal kidney cDNA library and isolated several clones representing two differently spliced mRNA transcripts, designated ZNF236a and -b. Both transcripts were identical apart from the presence of an additional exon in ZNF236a that truncates the open reading frame. RT-PCR analysis confirmed the expression of both transcripts to be upregulated in human mesangial cells in response to elevated levels of d-glucose. ZNF236a and -b cDNAs encode polypeptides of 174 and 204 kDa, containing 25 and 30 C(2)H(2) zinc-finger motifs, respectively. Northern blot analysis showed that ZNF236 is ubiquitously expressed in all human tissues tested. Expression levels were highest in skeletal muscle and brain, intermediate in heart, pancreas, and placenta, and lowest in kidney, liver, and lung. Southern zoo blot analysis indicated that ZNF236 is conserved in the genomes of all mammalian species tested, but not in yeast. The mapping of ZNF236 to human chromosome 18q22-q23, close to the IDDM6 locus, coupled with the glucose-regulated expression of the gene in human mesangial cells, suggests that ZNF236 may be a candidate gene for diabetic nephropathy.

Holmes DI ，Wahab NA ，Mason RM 《GENOMICS》

Cloning and characterization of ZNF189, a novel human Krüppel-like zinc finger gene localized to chromosome 9q22-q31.

Odeberg J ，Røsok O ，Gudmundsson GH ，Ahmadian A ，Roshani L ，Williams C ，Larsson C ，Pontén F ，Uhlén M ，Asheim HC ，Lundeberg J ... -  《GENOMICS》

Isolation, characterization, and mapping of a zinc finger gene, ZFP95, containing both a SCAN box and an alternatively spliced KRAB A domain.

A new zinc finger gene of the Krüppel family was identified by screening a human fetal cartilage cDNA library with degenerate oligonucleotides. Sequence analysis indicates that ZFP95 contains 12 highly conserved zinc finger motifs at the C-terminus and a SCAN box as well as a KRAB A domain at the N-terminus of the protein. ZFP95 represents a member of a new subclass of Krüppel zinc finger proteins containing both a SCAN box and a KRAB domain. Sequence comparison revealed that ZFP95 is the human ortholog of murine Zfp95, which is differentially expressed during spermatogenesis. We demonstrate that ZFP95 is ubiquitously expressed in adult and fetal tissues with the strongest expression in testis. Two transcripts, 4. 2 and 4.6 kb, were detected in all tissues tested. In testis, a third transcript of 3.8 kb was present. RT-PCR analysis confirmed alternative splicing for the KRAB A domain and an upstream exon leading to three transcripts of ZFP95 with and without this transcriptional repressor domain. Finally, we show that ZFP95 maps on human chromosome 7q22 between the markers D7S651 and WI-5853.

Dreyer SD ，Zheng Q ，Zabel B ，Winterpacht A ，Lee B ... -  《GENOMICS》