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Transcriptional activation of the type II transforming growth factor-beta receptor gene upon differentiation of embryonal carcinoma cells.
J Biol Chem. 1998 Aug 14; 273(33):21115-24.JB

Abstract

Previously, it has been shown that differentiation of embryonal carcinoma (EC) cells turns on the expression of functional transforming growth factor type-beta receptors. Here, we show that the type II receptor (TbetaR-II) gene is activated at the transcriptional level when EC cells differentiate. We show that the differentiated cells, but not the parental EC cells, express transcripts for TbetaR-II. In addition, the expression of TbetaR-II promoter/reporter gene constructs are elevated dramatically when EC cells differentiate and we identify at least two positive and two negative regulatory regions in the 5' flanking region of the TbetaR-II gene. Moreover, we identify a cAMP response element/activating transcription factor site that acts as a positive cis-regulatory element in the TbetaR-II promoter, and we demonstrate that the transcription factor ATF-1 binds to this site and strongly stimulates the expression of the TbetaR-II promoter/reporter gene constructs when ATF-1 is overexpressed in EC-derived differentiated cells. Equally important, we identify a negative regulatory element in a 53-base pair region that had previously been shown to inhibit strongly the expression of TbetaR-II promoter/reporter gene constructs. Specifically, we demonstrate that this region, which contains an inverted CCAAT box motif, binds the transcription factor complex NF-Y (also referred to as CBF) in vitro. Furthermore, expression of a dominant-negative NF-YA mutant protein, which prevents DNA binding by NF-Y, enhances TbetaR-II promoter expression. Together, these studies suggest that the transcription factors ATF-1 and NF-Y play important roles in the regulation of the TbetaR-II gene.

Authors+Show Affiliations

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9694866

Citation

Kelly, D, et al. "Transcriptional Activation of the Type II Transforming Growth Factor-beta Receptor Gene Upon Differentiation of Embryonal Carcinoma Cells." The Journal of Biological Chemistry, vol. 273, no. 33, 1998, pp. 21115-24.
Kelly D, Kim SJ, Rizzino A. Transcriptional activation of the type II transforming growth factor-beta receptor gene upon differentiation of embryonal carcinoma cells. J Biol Chem. 1998;273(33):21115-24.
Kelly, D., Kim, S. J., & Rizzino, A. (1998). Transcriptional activation of the type II transforming growth factor-beta receptor gene upon differentiation of embryonal carcinoma cells. The Journal of Biological Chemistry, 273(33), 21115-24.
Kelly D, Kim SJ, Rizzino A. Transcriptional Activation of the Type II Transforming Growth Factor-beta Receptor Gene Upon Differentiation of Embryonal Carcinoma Cells. J Biol Chem. 1998 Aug 14;273(33):21115-24. PubMed PMID: 9694866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional activation of the type II transforming growth factor-beta receptor gene upon differentiation of embryonal carcinoma cells. AU - Kelly,D, AU - Kim,S J, AU - Rizzino,A, PY - 1998/8/8/pubmed PY - 1998/8/8/medline PY - 1998/8/8/entrez SP - 21115 EP - 24 JF - The Journal of biological chemistry JO - J Biol Chem VL - 273 IS - 33 N2 - Previously, it has been shown that differentiation of embryonal carcinoma (EC) cells turns on the expression of functional transforming growth factor type-beta receptors. Here, we show that the type II receptor (TbetaR-II) gene is activated at the transcriptional level when EC cells differentiate. We show that the differentiated cells, but not the parental EC cells, express transcripts for TbetaR-II. In addition, the expression of TbetaR-II promoter/reporter gene constructs are elevated dramatically when EC cells differentiate and we identify at least two positive and two negative regulatory regions in the 5' flanking region of the TbetaR-II gene. Moreover, we identify a cAMP response element/activating transcription factor site that acts as a positive cis-regulatory element in the TbetaR-II promoter, and we demonstrate that the transcription factor ATF-1 binds to this site and strongly stimulates the expression of the TbetaR-II promoter/reporter gene constructs when ATF-1 is overexpressed in EC-derived differentiated cells. Equally important, we identify a negative regulatory element in a 53-base pair region that had previously been shown to inhibit strongly the expression of TbetaR-II promoter/reporter gene constructs. Specifically, we demonstrate that this region, which contains an inverted CCAAT box motif, binds the transcription factor complex NF-Y (also referred to as CBF) in vitro. Furthermore, expression of a dominant-negative NF-YA mutant protein, which prevents DNA binding by NF-Y, enhances TbetaR-II promoter expression. Together, these studies suggest that the transcription factors ATF-1 and NF-Y play important roles in the regulation of the TbetaR-II gene. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9694866/Transcriptional_activation_of_the_type_II_transforming_growth_factor_beta_receptor_gene_upon_differentiation_of_embryonal_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)48959-4 DB - PRIME DP - Unbound Medicine ER -