TY - JOUR
T1 - The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells
AU - Yang, Meng Chun
AU - Guo, Yuhong
AU - Liu, Chia Chi
AU - Weissler, Jonathan C.
AU - Yang, Yih Sheng
N1 - Funding Information:
We greatly appreciate Feitao Deng, Qiuying Hang, and Aaron Aldape for their excellent technical assistance. This work was supported by NHLBI Grant R01HL63525 to Y.S.Y., the Will Rogers Institute and the James M. Collins Center for Biomedical Research to J.C.W.
PY - 2006/6/2
Y1 - 2006/6/2
N2 - Surfactant protein-B (SP-B) and -C (SP-C) are small hydrophobic surfactant proteins that maintain surface tension in alveoli. Both SP-B and SP-C are regulated by a key factor, thyroid transcription factor-1 (TTF-1), in lung cells. Previously, we identified a 26-kDa, TTF-1-associated protein (TAP26) that was shown to interact with TTF-1 and enhance TTF-1-transactivated SP-B promoter activity. In this study, we hypothesized that TAP26 could also serve as a co-activator of the SP-C promoter. Using the chromatin immunoprecipitation assay (ChIP), we demonstrated that TAP26 was not only a component of the SP-B promoter, but was also a component of the SP-C promoter complex in lung cells. TAP26 could synergistically stimulate TTF-1-activated SP-B and SP-C promoter activities in H441 cells (a lung adenocarcinoma cell). However, in MLE12 cells (a murine lung type II cell), only SP-B, but not SP-C, promoter activity was improved by TAP26 in a concentration-dependent manner. This result indicated that the TTF-1/TAP26 complex-activated SP-C promoter activity was already optimized in MLE12 cells and that the response of the SP-C promoter to the complex was different from that of the SP-B promoter. Via promoter mutation analysis, adjacent TTF-1 binding sites within the proximal promoter region of SP-C were found to be essential for TTF-1/TAP26-enhanced SP-C promoter activity. Thus, a dimerized complex structure was needed for advanced promoter activity. This result also provided a molecular mechanism by which both the SP-B and SP-C promoters could be differentially regulated by the same complex.
AB - Surfactant protein-B (SP-B) and -C (SP-C) are small hydrophobic surfactant proteins that maintain surface tension in alveoli. Both SP-B and SP-C are regulated by a key factor, thyroid transcription factor-1 (TTF-1), in lung cells. Previously, we identified a 26-kDa, TTF-1-associated protein (TAP26) that was shown to interact with TTF-1 and enhance TTF-1-transactivated SP-B promoter activity. In this study, we hypothesized that TAP26 could also serve as a co-activator of the SP-C promoter. Using the chromatin immunoprecipitation assay (ChIP), we demonstrated that TAP26 was not only a component of the SP-B promoter, but was also a component of the SP-C promoter complex in lung cells. TAP26 could synergistically stimulate TTF-1-activated SP-B and SP-C promoter activities in H441 cells (a lung adenocarcinoma cell). However, in MLE12 cells (a murine lung type II cell), only SP-B, but not SP-C, promoter activity was improved by TAP26 in a concentration-dependent manner. This result indicated that the TTF-1/TAP26 complex-activated SP-C promoter activity was already optimized in MLE12 cells and that the response of the SP-C promoter to the complex was different from that of the SP-B promoter. Via promoter mutation analysis, adjacent TTF-1 binding sites within the proximal promoter region of SP-C were found to be essential for TTF-1/TAP26-enhanced SP-C promoter activity. Thus, a dimerized complex structure was needed for advanced promoter activity. This result also provided a molecular mechanism by which both the SP-B and SP-C promoters could be differentially regulated by the same complex.
KW - Gene regulation
KW - Surfactant protein-B
KW - Surfactant protein-C
KW - TAP26
KW - TTF-1
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U2 - 10.1016/j.bbrc.2006.03.158
DO - 10.1016/j.bbrc.2006.03.158
M3 - Article
C2 - 16630564
AN - SCOPUS:33646082255
SN - 0006-291X
VL - 344
SP - 484
EP - 490
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -