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
D I
DI
Division of Biomedical Sciences, Imperial College School of Medicine, BMS Building, South Kensington, London, SW7 2AZ, United Kingdom.
Wahab
N A
NA
Mason
R M
RM
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C121390:ZNF236 protein, human; D005947:Glucose