Cis-regulatory elements and transcription factors involved in the regulation of the transforming growth factor-β2 gene

B. Scholtz, D. Kelly, A. Rizzino

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Embryonal carcinoma (EC) cells and embryonic stem (ES) cells provide useful model systems for studying differentiation during early mammalian development. Previous studies have demonstrated that differentiation of two restricted mouse EC cell lines is accompanied by activation of the TGF-β2 gene. Moreover, one negative and two positive regulatory regions upstream of the transcription start site were identified, which appear to play key roles in the transcriptional regulation of the human TGF-β2 gene. In this report, we demonstrate that the same three regulatory regions strongly influence the activity of the TGF-β2 promoter in differentiated cells derived from the multipotent human EC cell line, NT2/D1, and from the murine totipotent ES cell line, CCE. We also determined that the same three regions are active in the regulation of the TGF-β2 gene in the murine parietal endoderm-like cell line, PYS-2. However, an additional negative regulatory region appears to contribute to the regulation of the TGF-β2 gene in PYS-2 cells. Last, mutation of a CRE/ATF element located just upstream of the transcription start site of the TGF-β2 gene reduces significantly the activity of the TGF- β2 promoter in the differentiated cells. However, in contrast to our previous findings, our gel mobility shift analyses demonstrate that this CRE/ATF element is bound by similar proteins in nuclear extracts prepared from undifferentiated and differentiated mouse EC cells as well as from undifferentiated human EC cells. Taken together, our findings suggest strongly that four regulatory regions, including a critical CRE/ATF element, help control the expression of the TGF-β2 gene during early mammalian development.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalMolecular Reproduction and Development
Volume41
Issue number2
DOIs
Publication statusPublished - 1995

Fingerprint

Embryonal Carcinoma Stem Cells
Transforming Growth Factors
Transcription Factors
Nucleic Acid Regulatory Sequences
Genes
Cell Line
Transcription Initiation Site
Embryonic Stem Cells
Totipotent Stem Cells
Endoderm
Electrophoretic Mobility Shift Assay
Nuclear Proteins
Mutation

Keywords

  • Activating transcription factor
  • Differentiation
  • Embryonal carcinoma cells
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Cis-regulatory elements and transcription factors involved in the regulation of the transforming growth factor-β2 gene. / Scholtz, B.; Kelly, D.; Rizzino, A.

In: Molecular Reproduction and Development, Vol. 41, No. 2, 1995, p. 140-148.

Research output: Contribution to journalArticle

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