scholarly journals GATA-6 and Thyroid Transcription Factor-1 Directly Interact and Regulate Surfactant Protein-C Gene Expression

2001 ◽  
Vol 277 (6) ◽  
pp. 4519-4525 ◽  
Author(s):  
Cong Liu ◽  
Stephan W. Glasser ◽  
Huajing Wan ◽  
Jeffrey A. Whitsett
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Protein C ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

scholarly journals Nuclear localization domain of thyroid transcription factor-1 in respiratory epithelial cells

1997 ◽  
Vol 328 (3) ◽  
pp. 757-761 ◽  
Author(s):  
Manely GHAFFARI ◽  
Xin ZENG ◽  
A. Jeffrey WHITSETT ◽  
Cong YAN
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Nuclear Localization ◽  
Nuclear Translocation ◽  
Surfactant Protein ◽  
Thyroid Transcription Factor 1 ◽  
Surfactant Protein B ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Thyroid transcription factor-1 (TITF-1) is a homeodomain containing transcription factor that binds to and selectively activates the expression of genes in thyroid and pulmonary epithelial cells. TITF-1 plays a critical role in gene expression and in organogenesis of lung and thyroid. In the present work, epitope-tagged TITF-1 proteins were used to identify the regions of the TITF-1 polypeptide that mediate nuclear localization and transcriptional activity in human lung adenocarcinoma cells. A series of TITF-1-flag deletion mutants was generated and transfected into H441 cells to determine amino acid sequences involved in translocation to the nucleus. Transfection of the TITF-1-flag mutants demonstrated that a nuclear localization signal (NLS) sequence, located at the N-terminus of the homeodomain, is critical for nuclear targeting. The NLS was essential but not sufficient for translocation of TITF-1 to the nucleus, since deletion of the homeodomain itself also blocked nuclear translocation in the presence of NLS. Deletion of the N-terminal transactivation domain of TITF-1 completely abolished its transcriptional activation on the human surfactant protein-B promoter, and deletion of the C-terminal domain partially reduced its stimulatory activity. Nuclear translocation of TITF-1 depends on both an NLS and the homeodomain of the polypeptide. Both C- and N-terminal regions of TITF-1 are involved in transactivation of surfactant protein B gene expression in pulmonary cells.

scholarly journals Nuclear Factor I/Thyroid Transcription Factor 1 Interactions Modulate Surfactant Protein C Transcription

2003 ◽  
Vol 23 (24) ◽  
pp. 9014-9024 ◽  
Author(s):  
Cindy J. Bachurski ◽  
Guan Hu Yang ◽  
Tracey A. Currier ◽  
Richard M. Gronostajski ◽  
Dihua Hong
Keyword(s):  
Protein C ◽  
Family Members ◽  
Surfactant Protein ◽  
Type Ii ◽  
Dimerization Domain ◽  
Surfactant Protein C ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Nuclear Factor I ◽  
Transcription Factor 1

ABSTRACT Surfactant protein C (SP-C; Sftpc) gene expression is restricted to pulmonary type II epithelial cells. The proximal SP-C promoter region contains critical binding sites for nuclear factor I (NFI) and thyroid transcription factor 1 (TTF-1; also called Nkx2.1). To test the hypothesis that NFI isoforms interact with TTF-1 to differentially regulate SP-C transcription, we performed transient transfection assays in JEG-3 cells, a choriocarcinoma cell line with negligible endogenous NFI or TTF-1 activity. Cotransfection of NFI family members with TTF-1 induced synergistic activation of the SP-C promoter that was further enhanced by p300. TTF-1 directly interacts with the conserved DNA binding and dimerization domain of all NFI family members in coimmunoprecipitation and mammalian two-hybrid experiments. To determine whether SP-C expression is regulated by NFI in vivo, a chimeric fusion protein containing the DNA binding and dimerization domain of NFI-A and the Drosophila engrailed transcriptional repression domain (NFIen) was conditionally expressed in mice under control of a doxycycline-inducible transgene. Induction of NFIen in a subset of type II cells inhibited SP-C gene expression without affecting expression of TTF-1 in doxycycline-treated double-transgenic mice. Taken together, these findings support the hypothesis that NFI family members interact with TTF-1 to regulate type II cell function.

scholarly journals Modulation of Thyroid-Specific Gene Expression in Normal and Nodular Human Thyroid Tissues from Adults: An in Vivo Effect of Thyrotropin

2005 ◽  
Vol 90 (10) ◽  
pp. 5692-5697 ◽  
Author(s):  
Rocco Bruno ◽  
Elisabetta Ferretti ◽  
Emanuele Tosi ◽  
Franco Arturi ◽  
Paolo Giannasio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Human Thyroid ◽  
Normal Tissues ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Group 2 ◽  
Transcription Factor 1 ◽  
Tsh Levels

Context: Evidence from in vitro studies or animal models has shown that TSH affects thyrocytes by thyroid-specific expression modulation. Objective: The objective of our study was to analyze the role of TSH in human thyroid gene expression in vivo. Design/Setting: Thirty-nine normal thyroid tissues were collected at the same center. Study Subjects: Patients were divided into two groups based on serum TSH levels: 17 with normal TSH levels (1–4 mU/liter; group 1) and 22 with TSH levels below 0.5 mU/liter (group 2). Intervention: Group 2 underwent thyroidectomy after suppressive l-T4 therapy. Main Outcome Measures: mRNA levels of thyroid genes such as sodium/iodide symporter (NIS), apical iodide transporter, pendrin, thyroglobulin, thyroperoxidase, TSH receptor, paired box transcription factor 8, and thyroid transcription factor-1 were evaluated by quantitative PCR. Results: The reduction of TSH stimulation causes decreases in NIS and apical iodide transporter gene expression in normal tissues and more limited reductions in thyroglobulin, thyroperoxidase, and paired box transcription factor 8, but it has no significant effect on TSH receptor, pendrin, or thyroid transcription factor-1. Comparison of NIS levels in normal and nodular tissues from the same patient confirmed that it is differentially expressed in nodules only in the presence of normal TSH (P < 0.01). In patients with suppressed TSH, nodular NIS levels were similar to those in normal tissues. Conclusions: Our data represent the first demonstration in human thyroid tissues that TSH contributes to the regulation of thyrocyte differentiation by modulating thyroid gene levels. It exerts a particularly important effect on the transcription of NIS, which becomes very low after prolonged TSH suppression.

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