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Cell Type-specific Expression (cell + type-specific_expression)
Selected AbstractsEvidence for local control of gene expression in the epidermal differentiation complex,EXPERIMENTAL DERMATOLOGY, Issue 5 2002James T. Elder Abstract: The epidermal differentiation complex (EDC), located on chromosomal band 1q21, consists of at least 43 genes that are expressed during keratinocyte differentiation. Indicative of a role for chromatin structure in tissue specificity of EDC gene expression, we identified an inverse correlation between expression and DNA methylation for two EDC genes (S100A2 and S00A6) in human keratinocytes and fibroblasts. 5-azacytidine (5AC) and sodium butyrate (NaB) are two agents known to promote ,open' chromatin structure. To explore the relationship between chromatin structure and keratinocyte differentiation, we treated normal human keratinocytes (NHK) with 5AC or NaB, or with protocols known to promote their terminal differentiation. We then measured the steady-state mRNA levels for several S100 genes, small proline rich region-1, -2, and -3, loricrin, and involucrin by Northern blotting. 5AC and NaB each markedly increased expression of SPRR1/2 and involucrin in NHK. In contrast, expression of S100A2 was reduced by both agents, and by induction of keratinocyte differentiation. Moreover, while the clustered EDC genes displayed a general tendency to be expressed in epithelial cells, they displayed different patterns of cell type-specific expression. These results indicate that local, gene-specific factors play an important role in the regulation of EDC gene expression in the keratinocyte lineage and during keratinocyte terminal differentiation. [source] Transcription factors NF-,B and Sp1 are major determinants of the basal promoter activity of the rat GD3-synthase geneJOURNAL OF NEUROCHEMISTRY, Issue 2002G. Zeng GD3-synthase is one of the key sialyltransferases responsible for synthesis of ganglioside GD3, the substrate for initiation of the ,b' and ,c' series ganglioside synthesis. We have previously cloned the rat GD3-synthase gene promoter, and preliminary characterization has identified a minimal 0.5-kb region that has a strong basal promoter activity, and is GC-rich and has no CAAT or TATA boxes. In this study, we showed that the Sp1 and NF-,B sites in this region significantly contributed to basal GD3-synthase promoter activity. When either the Sp1 or NF-,B sites were deleted, a 50% decrease in promoter activity was observed. The same results were obtained by a decoy strategy using oligonucleotides containing the Sp1 or NF-,B sites. The binding to the Sp1 and NF-,B sites was confirmed by electrophoretic mobility shift assay (EMSA), competition and supershift EMSA. In addition, cell-type specific activation of the promoter was also determined. The promoter was highly activated in the GD3-expressing F-11 cells while repressed in NG-108 cells in which GD3 is almost undetectable. An additional band of NF-,B family was identified only in the F-11 nuclear extract using the NF-,B consensus probe by EMSA. DNA pull-down assays were further carried out to screen proteins that bound to the promoter including the basal region and the potential negative-regulatory region between ,526 and ,769. More than 10 major binding proteins were pulled down, some of which were present only in the F-11 or NG-108 nuclear extracts. Our data demonstrate that NF-,B and Sp1 are the major determinants for the basal promoter activity and some factors such as NF-,B may be involved in cell type-specific expression of the gene. [source] From the Background to the Spotlight: TASK Channels in Pathological ConditionsBRAIN PATHOLOGY, Issue 6 2010Stefan Bittner Abstract TWIK-related acid-sensitive potassium channels (TASK1,3) belong to the family of two-pore domain (K2P) potassium channels. Emerging knowledge about an involvement of TASK channels in cancer development, inflammation, ischemia and epilepsy puts the spotlight on a leading role of TASK channels under these conditions. TASK3 has been especially linked to cancer development. The pro-oncogenic potential of TASK3 could be shown in cell lines and in various tumor entities. Pathophysiological hallmarks in solid tumors (e.g. low pH and oxygen deprivation) regulate TASK3 channels. These conditions can also be found in (autoimmune) inflammation. Inhibition of TASK1,2,3 leads to a reduction of T cell effector function. It could be demonstrated that TASK1,/, mice are protected from experimental autoimmune inflammation while the same animals display increased infarct volumes after cerebral ischemia. Furthermore, TASK channels have both an anti-epileptic as well as a pro-epileptic potential. The relative contribution of these opposing influences depends on their cell type-specific expression and the conditions of the cellular environment. This indicates that TASK channels are per se neither protective nor detrimental but their functional impact depends on the "pathophysiological" scenario. Based on these findings TASK channels have evolved from "mere background" channels to key modulators in pathophysiological conditions. [source] Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human ,-Fetoprotein GeneCANCER SCIENCE, Issue 3 2000Michito Kunitomi We constructed a plasmid containing human ,-fetoprotein (AFP) promoter/enhancer to direct the cell type-specific expression of diphtheria toxin fragment A (DTA), designated as pAF-DTA, to AFP-producing hepatocellular carcinoma cells. The transfection was carried out with cationic liposomes (DMRIE-C) and the expression of the DTA gene was confirmed by a northern blot analysis. When pAF-DTA was transfected, the growth of AFP-positive HuH-7 cells was inhibited, whereas growth inhibition was not observed in AFP-negative MKN45 cells. In this experiment, the secretion of AFP was similarly suppressed, but the secretion of carcinoembryonic antigen from MKN45 was not altered. pAF-DTA could also exert its growth inhibitory effect on PLC, a cell line with a low level of AFP. However, no inhibitory effect of pAF-DTA was observed on the proliferation of primary hepatocyte cells. Furthermore, transfection experiments in which HuH-7 and splenic stromal cells were co-cultured revealed the growth inhibition by pAF-DTA to be selective in HuH-7 cells. Finally, the growth of HuH-7 transplanted on BALB/c nu/nu mice was inhibited by the direct injection of pAF-DTA/liposome complex into a tumor mass. These results suggest that use of pAF-DTA may be potentially useful as a novel approach for the selective treatment of tumor cells producing AFP even at low levels, without affecting other types of cells. [source] | ||||||||||