Nucleic Acids Research, Vol 26, Issue 22 5163-5169, Copyright © 1998 by Oxford University Press
P Mummaneni, P Yates, J Simpson, J Rose and MS Turker
The promoter region of the mouse adenine phosphoribosyltransferase (aprt)
gene contains one non-consensus Sp1 binding site at its 5' end followed by
three consensus Sp1 binding sites. The two 3'-most binding sites are
sufficient for maximal expression of aprt , suggesting that the
non-consensus and consensus binding sites at the 5' end are redundant.
However, the two 3' sites are not sufficient to block epigenetic
inactivation, which led to the hypothesis that the redundant consensus
and/or non-consensus 5' Sp1 binding sites are required to block
inactivation events. To test this hypothesis, promoter region constructs
were made in which the two 5' Sp1 binding sites were mutated alone or in
tandem, and then each construct was tested for its ability to withstand
epigenetic inactivation. A cis -acting methylation center that is normally
located 1.2 kb upstream of the promoter was used to induce inactivation.
The results demonstrate that the presence of the redundant consensus Sp1
binding site is required to block methylation- associated gene
inactivation. Therefore, the Sp1 binding sites comprising the mouse aprt
promoter have evolved two distinct functions, one to promote transcription
and the other to block epigenetic inactivation.
ARTICLES
The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation
Department of Pathology, University of Kentucky, Lexington, KY 40536, USA.
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