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J. Biol. Chem., Vol. 276, Issue 28, 25647-25650, July 13, 2001
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Gene Transcription in Mouse Embryonic Stem
Cells*,
,,¶
From the BRCA1 gene is a tumor suppressor for
breast and ovarian cancers with the putative role in DNA repair and
transcription. To characterize the role of BRCA1 in transcriptional
regulation, we analyzed gene expression profiles of mouse embryonic
stem cells deficient in BRCA1 using microarray technology. We
found that loss of BRCA1 correlated with decreased expression of
several groups of genes including stress response genes, cytoskeleton genes, and genes involved in protein synthesis and degradation. Previous study showed that BRCA1 is a transcriptional co-activator of
p53 protein; however the majority of p53 target genes remained at the
same expression levels in BRCA1 knockout cells as in the wild type
cells. The only p53 target gene down-regulated with the loss of BRCA1
was 14-3-3 Section of Molecular Signaling and
Oncogenesis, Division of Clinical Sciences, NCI, National
Institutes of Health, Bethesda, Maryland, 20892 and the
§ Curriculum in Genetics and Molecular Biology and the
Lineberger Comprehensive Cancer Center, University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina 27599
, a major G2/M checkpoint control gene.
Similar to cells with decreased 14-3-3 activity, BRCA1-deficient cells were unable to sustain G2/M growth arrest after
exposure to ionizing radiation. We find that BRCA1 induction of
14-3-3 requires the presence of wild type p53 and can be regulated
by a minimal p53 response element.
The on-line version of this article (available at
http://www.jbc.org) contains Table I.
¶
To whom correspondence should be addressed: ATC Bldg., Rm.
121, 8717 Grovemont Cr., Gaithersburg, MD 20878. Tel.: 301-435-5774; Fax: 301-402-3134; E-mail: apreliko@mail.nih.gov.
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