Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UID6 (Kruppel-like)
 147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wound repair in the liver induces altered gene expression in stellate cells (resident mesenchymal cells) in a process known as "activation." A zinc finger transcription factor cDNA, zf9, was cloned from rat stellate cells activated in vivo. Zf9 expression and biosynthesis are increased markedly in activated cells in vivo compared with cells from normal rats ("quiescent" cells). The factor is localized to the nucleus and the perinuclear zone in activated but not quiescent cells. Zf9 mRNA also is expressed widely in nonhepatic adult rat tissues and the fetal liver. The zf9 nucleotide sequence predicts a member of the Kruppel-like family with a unique N-terminal domain rich in serine-proline clusters and leucines. The human zf9 gene maps to chromosome 10P near the telomere. Zf9 binds specifically to a DNA oligonucleotide containing a GC box motif. The N-terminal domain of Zf9 (amino acids 1-201) is transactivating in the chimeric GAL4 hybrid system. In Drosophila schneider cells, full length Zf9 transactivates a reporter construct driven by the SV40 promoter/enhancer, which contains several GC boxes. A physiologic role for Zf9 is suggested by its transactivation of a collagen alpha1(I) promoter reporter. Transactivation of collagen alpha1(I) by Zf9 is context-dependent, occurring strongly in stellate cells, modestly in Hep G2 cells, and not at all in D. schneider cells. Our results suggest that Zf9 may be an important signal in hepatic stellate cell activation after liver injury.
 ...
PMID:Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. 968 9

The ZNF219 gene is a member of the Kruppel-like zinc finger gene family that is involved in a diverse range of biological processes. The ZNF219 gene encodes a 77-kDa nuclear protein containing nine sets of C2H2 zinc finger structures. By using a random oligonucleotide selection assay and the electromobility gel shift assay, we have revealed that the ZNF219 protein recognizes two copies of CCCCCA. The DNA binding core element is CCCCC. 3' flanking A residues enhance binding of the ZNF219 protein. Use of the various truncated ZNF219 constructs demonstrated that zinc finger 1 to 3 or zinc finger 5 and 6 domains are sufficient to allow specific DNA binding. Both domains independently recognized the same consensus sequence, CCCCCA. Proteins expressed from human cDNA clones KIAA0390 and KIAA0222, which have partial similarities to ZNF219, also showed specific binding to the same core DNA sequence. Potential ZNF219 binding sites were found in the HMGN1 promoter. To examine the function of ZNF219 in the modulation of transcription, we constructed Gal4 DNA binding domain (DBD)/ZNF219 fusion proteins and demonstrated that ZNF219 functioned as a transcriptional repressor for the HMGN1 promoter. Experiments with the truncated ZNF219 constructs suggest that the proline-rich sequence (226-272 a.a., proline content 49%) was responsible for part of the observed repression. These findings provide us with an important start point in our understanding of the functional role of ZNF219 in vivo.
 ...
PMID:Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor. 1462 Dec 94