Disease relevance of Tcf8

• It thus appears deltaEF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease [1].
• Two Zfhep antisense oligonucleotides repressed proliferation of either U-138 or U-343 glioblastoma cells more than control oligonucleotides [2].

High impact information on Tcf8

• In contrast, this element was repressed by the binding of the zinc-finger protein deltaEF1/ZEB1 [3].
• We propose a model of regulation where the activating transcription factor Nkx2.5 and the repressor deltaEF1/ZEB1 compete for an overlapping DNA binding site [3].
• The transcription factor deltaEF1 is inversely expressed with type II collagen mRNA and can repress Col2a1 promoter activity in transfected chondrocytes [4].
• Overexpression of deltaEF1 in differentiated chondrocytes resulted in decreased expression of a reporter construct containing a collagen II promoter/enhancer insert; however, this negative regulation was not dependent on the proximal E2 box [4].
• Chick limb bud mesenchymal cells, which do not express type II collagen, expressed abundant deltaEF1 mRNA, but, following differentiation in micromass culture, deltaEF1 mRNA expression was lost [4].

Biological context of Tcf8

• Coexpression of the wtS-(-306-OCluc) fusion gene with deltaEF1 decreased luciferase activity 30% relative to cotransfection with empty vector [5].
• Repression was abolished by point mutations in the putative deltaEF1 motifs, mS-(-306-OCluc) [5].
• To assess if overexpression of deltaEF1 augments transcriptional repression by these sequences, the intron 1 sequences (wtS) were placed upstream to the native rat osteocalcin promoter fused to a luciferase reporter gene (-306-OCluc) [5].
• The consensus sequence for the transcription factor deltaEF1 is homologous to two pyrimidine-rich repeats in intron 1 that contribute to silencing of osteocalcin-reporter fusion genes [5].
• To determine whether deltaEF1 binds to these DNA sequences, gel retardation assays were performed using oligonucleotides containing the putative osteocalcin deltaEF1 motifs and a classical deltaEF1 motif, as radiolabeled probes [5].

Anatomical context of Tcf8

• Primary embryonic chick sternal chondrocytes, which express abundant type II collagen, displayed minimal levels of deltaEF1 mRNA [4].
• We examined expression of Zfhep in the rat forebrain during embryonic and postnatal development [2].
• Interactions of non-receptor transcription factors (such as Zfhep) with certain TREs are important to modify gene-specific regulation by thyroid hormones [6].
• Expression of Zfhep in the ventricular zone decreases during late development as the population of progenitor cells decreases [2].
• We investigated a possible link between Zfhep and proliferation by treating human glial cell lines with Zfhep antisense phosphorothioate oligodeoxynucleotides [2].

Associations of Tcf8 with chemical compounds

• Bacterial lipopolysaccharide stimulates the thyrotropin-dependent thyroglobulin gene expression at the transcriptional level by involving the transcription factors thyroid transcription factor-1 and paired box domain transcription factor 8 [7].
• We screened for transcription factors that bind the rat (r) glycoprotein hormone alpha-subunit TRE (alpha-sub), and isolated a cDNA, termed zinc finger homeodomain enhancer-binding protein (Zfhep), which encodes two separate zinc finger domains (ZD1 and ZD2), and a region similar to homeodomains [6].
• Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damage-inducible 45 alpha (GADD 45 alpha), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8 [8].
• We extended our studies on Zfhep mRNA expression to cells of vascular origin (coronary endothelial cells [CECs]), that express AT(1) and AT(2) receptors, and that respond differently to Ang II dependent on which receptor subtype is stimulated [9].
• In quiescent PC12w cells, Zfhep mRNA was time-dependently induced by Ang II (10(-7) mol/L) up to 3 hours, an effect that was blocked by the selective AT(2) antagonist PD123177 (10(-6) mol/L) [9].

Regulatory relationships of Tcf8

• Chromatin immunoprecipitation assays and knockdown experiments showed that deltaEF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling [1].

Other interactions of Tcf8

• Here we present evidence that the transcription factor deltaEF1 participates in the negative regulation of Col2a1 transcription [4].
• To elucidate the mechanism of TSH/cAMP-mediated regulation of NIS gene expression, we have characterized the putative cAMP response element (CRE)/activator protein (AP)-1 site (termed NUC) that is closely located between the two Pax-8 (paired box domain transcription factor-8) binding sites within NUE [10].
• In the presence of epidermal growth factor (EGF) a concordant expression pattern of Zfhep and AT(2) mRNA was observed with marked downregulation 6 hours after stimulation with EGF+Ang II [9].

Analytical, diagnostic and therapeutic context of Tcf8

• Among the polymerase chain reaction products isolated, we identified Zfhep, a zinc finger homoeodomain enhancer-binding protein and the angiotensin AT(2) receptor itself, both implicated in developmental processes [9].

References