Nucleic Acids Research, Vol 24, Issue 23 4700-4708, Copyright © 1996 by Oxford University Press
JH Lichy, M Majidi, J Elbaum and MM Tsai
Through a mutational analysis of a differentially regulated enhancer, we
present evidence that supports a role for the transcription factor YY1 in
tumor suppression in HeLa/fibroblast somatic cell hybrids. The human ST5
gene was previously shown to be expressed as three RNA species, 4.6, 3.1
and 2.8 kb in length. Whereas the two larger species are expressed at
similar levels in all cell lines examined, the 2.8 kb mRNA is expressed
specifically in non-tumorigenic hybrids. In this study, the basis for the
differential expression of this mRNA species was investigated. The message
was shown to originate from a promoter located within an intron of the ST5
gene. An enhancer located approximaely 1500 nt upstream of the start site
was required for cell type specific expression. Mutational analysis of this
enhancer revealed an AP1 site and five YY1 sites which were necessary for
full enhancer activity. Levels of YY1 DNA binding activity were found to be
as much as 6-fold higher in the non-tumorigenic cells relative to the
tumorigenic cells, while AP1 activity was similar in both cell types. These
results suggest that a signaling pathway targeting YY1 may play an
important role in tumor suppression in HeLa-fibroblast hybrids.
ARTICLES
Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1: evidence that YY1 plays a part in tumor suppression
Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. lichy@email.afip.osd.mil
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