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Cis‐regulatory elements and transcription factors involved in the regulation of the transforming growth factor‐β2 gene
Author(s) -
Scholtz Beáta,
Kelly David,
Rizzino Angie
Publication year - 1995
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.1080410204
Subject(s) - biology , transcription factor , gene , genetics , regulation of gene expression , transforming growth factor , trans acting , regulator gene , regulatory sequence , microbiology and biotechnology , mutant
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. © 1995 Wiley‐Liss, Inc.