Nucleic Acids Research, Vol 25, Issue 12 2293-2300, Copyright © 1997 by Oxford University Press
JK Taylor, T Levy, ER Suh and PG Traber
Cdx2 is a caudal-related homeodomain transcription factor that is expressed
in complex patterns during mouse development and at high levels in the
intestinal epithelium of adult mice. Cdx2 activates transcription of
intestinal gene promoters containing specific binding sites. Moreover, Cdx2
has been shown to induce intestinal differentiation in cell lines. In this
study, we show that Cdx2 is able to bind to two well defined enhancer
elements in the HoxC8 gene. We then demonstrate that Cdx2 is able to
activate transcription of heterologous promoters when its DNA binding
element is placed in an enhancer context. Furthermore, the ability to
activate enhancer elements is cell-line dependent. When the Cdx2 activation
domain was linked to the Gal4 DNA binding domain, the chimeric protein was
able to activate Gal4 enhancer constructs in an intestinal cell line, but
was unable to activate transcription in NIH3T3 cells. These data suggest
that there are cell-specific factors that allow the Cdx2 activation domain
to function in the activation of enhancer elements. We hypothesize that
either a co-activator protein or differential phosphorylation of the
activation domain may be the mechanism for intestinal cell line-specific
function of Cdx2 and possibly in other tissues in early development.
ARTICLES
Activation of enhancer elements by the homeobox gene Cdx2 is cell line specific
Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
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