Disease relevance of Titf1

• In the C6 glioma cell-line, TTF-1 activates the PACAP promoter in a dose-dependent manner [1].
• The upstream TTF-1 site acts as an enhancer when coupled to a heterologous simian virus-40 promoter-chloramphenicol acetyltransferase (CAT) chimera and transfected into FRTL-5 thyroid cells [2].
• RESULTS: The expression of the respiratory-specific transcription factor TTF-1 is conserved in the epithelium of the developing fistula tract in TEF [3].
• Expression of the lung-specific thyroid transcription factor (TTF-1) within the tracheoesophageal fistula of embryo rats exposed to Adriamycin [4].

Psychiatry related information on Titf1

• RNase protection assays showed that TTF-1 and angiotensinogen mRNA levels are simultaneously increased in the subfornical organ by water deprivation [5].

High impact information on Titf1

• A rat thyroglobulin promoter fragment, capable of directing thyroid-specific transcription, binds at least three different factors, TTF-1, TTF-2 and UFA, which are all present in nuclear extracts of the differentiated rat thyroid cell line FRTL-5 [6].
• TTF-1 and TTF-2 are FRTL-5 specific, as demonstrated by their absence in nuclear extracts prepared from cell lines that do not express any thyroid-differentiated function, while UFA is present in all cell lines tested [6].
• Major histocompatibility complex class I gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneously [7].
• Pendrin is a novel in vivo downstream target gene of the TTF-1/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells [8].
• TG mediates the repression of TTF-1 gene expression by decreasing NFI RNA and protein levels, as well as by altering the binding activity of NFI, which is redox controlled [9].

Biological context of Titf1

• TG acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the 5' flanking region of TTF-1 [7].
• We have cloned the TTF-1 gene from rat liver genomic library, and the exon/intron organization and the structure of the 5' flanking region were determined [10].
• This transactivation of PACAP by TTF-1 was totally removed when the core TTF-1 binding motif at -369 was deleted [1].
• Thyroid-specific expression and cyclic adenosine 3',5'-monophosphate autoregulation of the thyrotropin receptor gene involves thyroid transcription factor-1 [11].
• TTF-1 phosphorylation is important for binding and activity [11].

Anatomical context of Titf1

• RNase protection assays showed that TTF-1 and PACAP mRNAs have daily fluctuations in the rat hypothalamus [1].
• We recently found that TTF-1, a homeodomain-containing transcription factor essential for the development of the fetal diencephalon, is postnatally expressed in the hypothalamic area and plays a transcription regulatory role for certain neurohormones [1].
• In the lung, TTF-1 mRNA and protein are also present at the earliest stages of differentiation and are later confined to the bronchial epithelium [12].
• In the brain, TTF-1 appears to be restricted to structures of diencephalic origin, including the developing neurohypophysis [12].
• We now report that the subfornical organ, an important site of angiotensinogen synthesis, is an extra-hypothalamic site of TTF-1 expression [5].

Associations of Titf1 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 [13].
• Tumor necrosis factor-alpha regulation of thyroid transcription factor-1 and Pax-8 in rat thyroid FRTL-5 cells [14].
• Increases in serum TSH levels in the PTU or T4 treated animals did not always correlate with increases in this measure of increased Tg synthesis; and TSH levels did not always correlate with changes in TTF-1 RNA levels that would be expected to accompany increased Tg synthesis [15].
• Indeed, with a lowered GSH concentration, the overexpressed Pax-8 still activates transcription efficiently, whereas, on the contrary, the overexpressed TTF-1 does not recover its transactivation capability when the respective chimerical target sequences are used (C5 and BSAP) [16].
• If the expression vector encoded for TTF-1-ER, a fusion gene coding for the entire TTF-1 protein fused to the hormone-binding domain of the steroid receptor, under the control of the RSV promoter, thyroglobulin gene expression was controlled by estrogen [17].

Physical interactions of Titf1

• TTF-1 binding to the proximal region overlaps with that for a novel protein present in FRTL-5 cells which can also recognize the promoter-proximal region of Tg [18].
• The TTF-1 homeodomain binds to six of the seven putative binding domains observed in the 5'-flanking region of the PACAP gene [1].

Enzymatic interactions of Titf1

• Transfection of chimeric TSHR-CAT plasmids with the down- and/or up-stream TTF-1 site deleted reveals that the down-stream TTF-1 element functions in the absence of the up-stream element, but function of the up-stream site requires the down-stream TTF-1 element [2].
• Indeed, ERK directly phosphorylates TTF-1 at three serine residues, and concomitant mutation of these serines to alanines completely abolishes ERK-mediated phosphorylation both in vitro and in vivo [19].

Regulatory relationships of Titf1

• As one possibility, this suggested there might be a hitherto unrecognized suppressor of TTF-1 RNA levels and TSH-induced Tg synthesis in individual follicles [15].
• HNF-3 and TTF-1 transcription factors are known to stimulate SP-B transcription [20].

Other interactions of Titf1

• Regulation of pituitary adenylate cyclase-activating polypeptide gene transcription by TTF-1, a homeodomain-containing transcription factor [1].
• Protein-DNA binding studies did not reveal any effect of insulin/IGF-I on the ubiquitous transcription factor and the TTF-1 binding capacity [21].
• Expressions of TTF-1 messenger RNA and protein, which were assessed by Northern blot and Western blot analyses, respectively, were decreased by TNF-alpha treatment of FRTL-5 cells [14].
• Increased lung distension (due to CDH+TO) reduced expression of SP mRNAs and pro-SP-C and TTF-1 proteins and enhanced expression of RTI(40) (mRNA and protein; P < 0.05 for all) [22].
• We also investigated gene expression of the transcription factors PCNA, TTF-1, HNF3beta , GATA-6, C/EBPalpha and C/EBPdelta which drive, at least in part, development and differentiation of alveolar epithelium [23].

Analytical, diagnostic and therapeutic context of Titf1

• Double in situ hybridization histochemistry demonstrated the presence of TTF-1 mRNA in angiotensinogen-producing cells of the rat subfornical organ [5].
• Northern blot analysis revealed that TSH reduced TTF-1 mRNA abundance in a dose- and time-dependent manner [24].
• Immunoblotting analysis of FRTL-5 nuclear extracts does not show significant modification of the Pax-8 concentration in BSO-treated cells, whereas a decrease of 25% in TTF-1 protein is revealed [16].
• Analysis of the conformation and stability of rat TTF-1 homeodomain by circular dichroism [25].

References