Nucleic Acids Research, Vol 25, Issue 13 2661-2671, Copyright © 1997 by Oxford University Press
BD Hendrich, RM Plenge and HF Willard
The XIST gene in both humans and mice is expressed exclusively from the
inactive X chromosome and is required for X chromosome inactivation to
occur early in development. In order to understand transcriptional
regulation of the XIST gene, we have identified and characterized the human
XIST promoter and two repeated DNA elements that modulate promoter
activity. As determined by reporter gene constructs, the XIST minimal
promoter is constitutively active at high levels in human male and female
cell lines and in transgenic mice. We demonstrate that this promoter
activity is dependent in vitro upon binding of the common transcription
factors SP1, YY1 and TBP. We further identify two cis - acting repeated DNA
sequences that influence reporter gene activity. First, DNA fragments
containing a set of highly conserved repeats located within the 5'-end of
XIST stimulate reporter activity 3-fold in transiently transfected cell
lines. Second, a 450 bp alternating purine- pyrimidine repeat located 25 kb
upstream of the XIST promoter partially suppresses promoter activity by
approximately 70% in transient transfection assays. These results indicate
that the XIST promoter is constitutively active and that critical steps in
the X inactivation process must involve silencing of XIST on the active X
chromosome by factors that interact with and/or recognize sequences located
outside the minimal promoter.
ARTICLES
Identification and characterization of the human XIST gene promoter: implications for models of X chromosome inactivation
Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4955, USA.
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