Transcriptional regulation of the TGF-β2 gene in choriocarcinoma cells and breast carcinoma cells: Differential utilization of cis-regulatory elements

Michelle Kingsley-Kallesen, Lance Johnson, Beáta Scholtz, David Lee Kelly, A Angie Rizzino

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Previous studies have shown that the transcription of the TGF-β2 gene is controlled by at least one negative and two positive regulatory regions in differentiated cells derived from both embryonal carcinoma cells and embryonic stem cells. The use of TGF-β2 promoter/reporter gene constructs has also identified a CRE/ATF motif near the TATA box that appears to heavily influence the transcription of the TGF-β2 gene. In this study, two choriocarcinoma cell lines, JAR and JEG-3, and the breast cancer cell line, MCF-7, were used to determine whether differences exist in the transcriptional regulation of the TGF-β2 gene. We demonstrated that both similarities and differences exist in the transcriptional regulation of this gene. Common to all cells examined to date, the positive regulatory region just upstream of the TATA box contains an essential CRE/ATF motif that binds at least one transcription factor, ATF-1, in gel mobility shift assays. However, we did not detect ATF-2 binding to this site with any of the nuclear extracts used. We also determined that the effect of the region between - 187 and - 78 (relative to the transcription start site) is cell type dependent. Previous studies have shown that this region acts to reduce the activity of the TGF-β2 promoter in differentiated cells derived from embryonal carcinoma cells and embryonic stem cells. In direct contrast, this region acts as a strong positive regulatory region in JAR, JEG-3, and MCF-7 cells. The mechanisms responsible for these differing effects remain to be established. Interestingly, this region does not appear to contain sequence motifs that bind known transcription factors. Thus, this region is likely to bind one or more novel transcription factors or contain novel recognition sites for known transcription factors.

Original languageEnglish (US)
Pages (from-to)294-301
Number of pages8
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume33
Issue number4
DOIs
StatePublished - Apr 1997

Fingerprint

Choriocarcinoma
Nucleic Acid Regulatory Sequences
Genes
Cells
Breast Neoplasms
Embryonal Carcinoma Stem Cells
TATA Box
Transcription Factors
Embryonic Stem Cells
Transcription
Stem cells
Activating Transcription Factors
Cell Line
Transcription Initiation Site
MCF-7 Cells
Electrophoretic Mobility Shift Assay
Reporter Genes
Gels
Binding Sites
Assays

Keywords

  • ATF- 1
  • CRE/ATF motif
  • embryonal carcinoma cells
  • negative regulatory element
  • transcription factor

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

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title = "Transcriptional regulation of the TGF-β2 gene in choriocarcinoma cells and breast carcinoma cells: Differential utilization of cis-regulatory elements",
abstract = "Previous studies have shown that the transcription of the TGF-β2 gene is controlled by at least one negative and two positive regulatory regions in differentiated cells derived from both embryonal carcinoma cells and embryonic stem cells. The use of TGF-β2 promoter/reporter gene constructs has also identified a CRE/ATF motif near the TATA box that appears to heavily influence the transcription of the TGF-β2 gene. In this study, two choriocarcinoma cell lines, JAR and JEG-3, and the breast cancer cell line, MCF-7, were used to determine whether differences exist in the transcriptional regulation of the TGF-β2 gene. We demonstrated that both similarities and differences exist in the transcriptional regulation of this gene. Common to all cells examined to date, the positive regulatory region just upstream of the TATA box contains an essential CRE/ATF motif that binds at least one transcription factor, ATF-1, in gel mobility shift assays. However, we did not detect ATF-2 binding to this site with any of the nuclear extracts used. We also determined that the effect of the region between - 187 and - 78 (relative to the transcription start site) is cell type dependent. Previous studies have shown that this region acts to reduce the activity of the TGF-β2 promoter in differentiated cells derived from embryonal carcinoma cells and embryonic stem cells. In direct contrast, this region acts as a strong positive regulatory region in JAR, JEG-3, and MCF-7 cells. The mechanisms responsible for these differing effects remain to be established. Interestingly, this region does not appear to contain sequence motifs that bind known transcription factors. Thus, this region is likely to bind one or more novel transcription factors or contain novel recognition sites for known transcription factors.",
keywords = "ATF- 1, CRE/ATF motif, embryonal carcinoma cells, negative regulatory element, transcription factor",
author = "Michelle Kingsley-Kallesen and Lance Johnson and Be{\'a}ta Scholtz and Kelly, {David Lee} and Rizzino, {A Angie}",
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T2 - Differential utilization of cis-regulatory elements

AU - Kingsley-Kallesen, Michelle

AU - Johnson, Lance

AU - Scholtz, Beáta

AU - Kelly, David Lee

AU - Rizzino, A Angie

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AB - Previous studies have shown that the transcription of the TGF-β2 gene is controlled by at least one negative and two positive regulatory regions in differentiated cells derived from both embryonal carcinoma cells and embryonic stem cells. The use of TGF-β2 promoter/reporter gene constructs has also identified a CRE/ATF motif near the TATA box that appears to heavily influence the transcription of the TGF-β2 gene. In this study, two choriocarcinoma cell lines, JAR and JEG-3, and the breast cancer cell line, MCF-7, were used to determine whether differences exist in the transcriptional regulation of the TGF-β2 gene. We demonstrated that both similarities and differences exist in the transcriptional regulation of this gene. Common to all cells examined to date, the positive regulatory region just upstream of the TATA box contains an essential CRE/ATF motif that binds at least one transcription factor, ATF-1, in gel mobility shift assays. However, we did not detect ATF-2 binding to this site with any of the nuclear extracts used. We also determined that the effect of the region between - 187 and - 78 (relative to the transcription start site) is cell type dependent. Previous studies have shown that this region acts to reduce the activity of the TGF-β2 promoter in differentiated cells derived from embryonal carcinoma cells and embryonic stem cells. In direct contrast, this region acts as a strong positive regulatory region in JAR, JEG-3, and MCF-7 cells. The mechanisms responsible for these differing effects remain to be established. Interestingly, this region does not appear to contain sequence motifs that bind known transcription factors. Thus, this region is likely to bind one or more novel transcription factors or contain novel recognition sites for known transcription factors.

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