Disease relevance of Tcf1

• Addition of the vaccinia recombinant protein to rat spleen extracts results in activation of transcription of an LF-B1-dependent promoter [1].
• HNF-1 mRNA is not present in the dedifferentiated hepatoma variant, C2, but reappears upon selection for gluconeogenesis coincident with the re-expression of liver-specific genes [2].
• In contrast to in vitro studies, HNF1 and RXR/RAR-independent mechanisms appear to be more important in regulation of Mrp2 and Ntcp gene expression in endotoxemia [3].
• Transcription factor C/EBPbeta has been known to regulate a wide array of genes including those involved in the acute-phase response [4].
• The effect of hyperglycemia on HNF1 suggests that glucose affects albumin expression at the level of transcription [5].

Psychiatry related information on Tcf1

• Transcription factor genes that were expressed included inhibitors of DNA binding protein (Id) [6].

High impact information on Tcf1

• A myosin-like dimerization helix and an extra-large homeodomain are essential elements of the tripartite DNA binding structure of LFB1 [7].
• The cDNA was recombined into a vaccinia virus vector and active LF-B1 was obtained from infected HeLa cells [1].
• The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain [1].
• The sequence of the protein has been partially determined and, subsequently, overlapping cDNA clones containing the entire open reading frame of LF-B1 were isolated [1].
• Mutations in this region failed to activate alpha 1AT expression in nonhepatic cells, but mutations in the binding site for liver factor B1 (LF-B1) reduced hepatic-specific expression greater than 100-fold [8].

Chemical compound and disease context of Tcf1

• By replacing the serine/threonine-rich activation domain of LFB1 with the acidic activation domain of VP16, we generated transcription factors that act as dominant positive interfering mutants on endogenous LFB1 in differentiated hepatoma cells [9].
• As renal cell carcinomas are characterized by the disappearance of the transcription factor LFB1, which is known to be primarily involved in gene regulation in the liver, we have measured the presence of LFB1 in rat hepatocellular carcinomas induced by diethylnitrosamine [10].
• Expression of liver type pyruvate kinase in insulinoma cells: involvement of LF-B1 (HNF1) [11].
• We determined how HNF1 and IL6DEX-NP regulate rGSTA2 and albumin expression in rats during the acute phase response after LPS (lipopolysaccharide) treatment [12].
• Decreased expression levels of rat liver glutathione S-transferase A2 and albumin during the acute phase response are mediated by HNF1 (hepatic nuclear factor 1) and IL6DEX-NP [12].

Biological context of Tcf1

• Binding of the LFB1 dimer to a B-DNA palindromic consensus sequence requires either a conformational change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA [13].
• The helix-turn-helix motif, which has been shown to comprise the DNA recognition helix in the Antp homeodomain, can readily be recognized in the LFB1/HNF1 homeodomain, in spite of an extensive modification of the primary structure [14].
• A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain [15].
• However, activity was restored in the presence of the upstream elements, showing that cooperation with factors binding to the CCAAT box and distal elements favors the functional interaction of the liver-specific APF/HNF1 factor with lower-affinity binding sites [16].
• The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation [16].

Anatomical context of Tcf1

• Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes [15].
• Twenty-seven probe sets were present in both CBDL-derived beta2m-/Thy-1+ BM stem cells and control hepatocytes but absent in control beta2m-/Thy-1+ BM stem cells, including Tcf1 and Dbp [17].
• In vivo footprinting experiments show that the HNF1 binding site is similarly occupied in both adult liver and adult pancreas, in which this gene is practically inactive [18].
• Furthermore, the hybrid cells failed to express LF-B1-binding activity and mRNA [8].
• Run-on transcription analysis in isolated nuclei demonstrates that the expression of HNF1 in these cell lines is regulated primarily at the transcriptional level [19].

Associations of Tcf1 with chemical compounds

• These results suggest that transcription of the pyruvate kinase L gene is not simply regulated by the level of LF-B1 mRNA [20].
• When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased [21].
• However, inactivation of either cytokine led to preservation of HNF1 and partially of retinoid X receptor/retinoic acid receptor (RXR/RAR) binding activity [3].
• Our results show that LFB3 transcripts can be detected in mesoderm-derived cells as soon as they are induced to differentiate into a polarized epithelium, while LFB1 transcripts appear only at a later stage when the three different segments of the nephron become apparent [22].
• In light of our previous observation that diabetes decreases the abundance of hepatocyte nuclear factor 1 (HNF1), the predominant factor increasing albumin gene transcription, we wondered whether glucose normalization in diabetes would alter HNF1 [5].

Physical interactions of Tcf1

• The dihedral symmetry of DCoH suggests that binding to the dimerization domain of HNF-1 likely involves the superposition of two-fold rotation axes of the two proteins [23].
• Constitutive expression of the gene for the cell-specific p48 DNA-binding subunit of pancreas transcription factor 1 in cultured cells is under control of binding sites for transcription factors Sp1 and alphaCbf [24].
• In gel shift assays, HNF-1alpha and HNF-1beta in H4-II-E extracts bind to the palindromic HNF-1 site [25].
• Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain [26].

Regulatory relationships of Tcf1

• These results indicate that amylin is positively regulated by cAMP and PKA through the transcription factors HNF-1 and NFY [27].
• Transcription factor responses to either stimulus pattern were blocked by the noncompetitive NMDA receptor antagonist MK-801 [28].

Other interactions of Tcf1

• Peptides from the protein interacting with the albumin proximal element, or B box (APF), and the factor interacting with the alpha 1-antitrypsin promoter (LF-B1) are found in the predicted sequence of HNF-1 [2].
• The proximal 5'-flanking sequence of the L-PK gene therefore appears to function in vitro as an efficient liver-specific promoter which requires the binding of the liver factor HNF1 and which is also stimulated by the binding of another liver-specific factor, LF-A1 [29].
• Differentiation did not alter the frequency of association of the PLP gene with domains of myelin transcription factor 1 (Myt1), which binds the PLP promoter [30].
• In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment [31].
• Transcription factor STAT3 in leptin target neurons of the rat hypothalamus [32].

Analytical, diagnostic and therapeutic context of Tcf1

• Titration of HNF1 resulted in an 85% decrease of transcriptional activity, while titration of LF-A1 resulted in only a 40% decrease [29].
• Gel retardation assay indicated that the different trans-acting factors interacted with three elements and that the transacting protein bound to PKL-I was in fact LF-B1 [33].
• The L-PK mRNA level in rat liver changed after partial hepatectomy, during development and on intake of a high carbohydrate diet, while the level of LF-B1 mRNA remained unchanged or altered reciprocally [20].
• We have analyzed the expression pattern of LFB1 and LFB3 in the developing rat kidney by in situ hybridization [22].
• Immunoprecipitation and immunoblot analyses showed that C2 decreased the level of ubiquitinated HNF1, which was reversed by treatment with MG132, a proteasome inhibitor [34].

References