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)

Water channel aquaporin-1 (AQP1) is expressed in erythrocytes and various epithelia and endothelia. To study AQP1 gene regulation, human cell lines were screened for inducible AQP1 expression. Human erythroleukemia HEL cells showed AQP1 transcript expression on RNase protection assay. After butyrate-induced erythroid differentiation, AQP1 transcript expression increased strongly, producing water-permeable cells with plasma membrane localization of immunoreactive AQP1. In addition, a clonal subline of K562 cells [K562(S)] showed strong butyrate-induced expression of functional AQP1. A 1.8-kb DNA fragment of the 5' flanking region of the human AQP1 gene was isolated, sequenced, and analyzed functionally by the CAT reporter assay. The AQP1 promoter contained TATA and CCAAT boxes; Sp1, AP1, AP2, and E-box elements; and erythrocyte-specific CACCC and Kruppel-like (CCCCACCCA) elements. AQP1 promoter activity was more than 24-fold higher in HEL and K562(S) cells than in nonerythroid (HeLa) cells, indicating the presence of erythroid-specific factors. In K562(S) cells, CAT activities for promoter fragments to bp +23 [relative to beta-gal and normalized to 100% for the plasmid CP-282 (bp -282 to +23)] were 22 (-1779), 73 (-1402), 61 (-1129), 31 (-789), 87 (-487), 100 (-282), 73 (-229), 52 (-152), and 60% (-79). After butyrate-induced differentiation, CAT activities were stimulated approximately 10-fold for constructs -229/+23 and longer, compared to approximately 5-fold for -152/+23 and -79/+23; glucocorticoids did not affect CAT activities. These results suggest a basis for erythroid-specific AQP1 expression and the presence of a butyrate-response sequence involved in inducible AQP1 regulation in erythroleukemia cells.
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PMID:Isolation of the human aquaporin-1 promoter and functional characterization in human erythroleukemia cell lines. 948 Jul 47

Activation of hepatic stellate cells (HSCs) is the central event in the development of liver fibrosis and cirrhosis. The transdifferentiation process of quiescent into activated HSCs requires a complete reprogramming in gene expression, which is governed by modulation of transcriptional activators or repressors. Using microarray analysis to identify genes differentially expressed during the activation process of human HSCs, zinc finger protein 267 (ZNF267) mRNA was up-regulated in activated HSCs and in cirrhotic human liver. ZNF267 belongs to the family of Kruppel-like zinc fingers and contains a conserved KRAB (Kruppel associated box) A and B domain in the N-terminal part outside the C-terminal region of zinc fingers. ZNF267 constructs containing enhanced cyan fluorescence protein were constitutively localized in the nucleus. When fused to GAL4 DNA binding domain, full-length ZNF267 and all constructs encompassing KRAB A domain showed transcriptional repressor activity. Microarray analysis and RNase protection assays showed that ZNF267 represses MMP-10 gene expression, which was confirmed by reporter gene assays. Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo.
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PMID:Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10. 1605 93