Nucleic Acids Research, 1992, Vol. 20, No. 7 1769-1775
© 1992
MOLECULAR BIOLOGY |
A conserved region in intron 1 negatively regulates the expression of the PCNA gene
Jefferson Cancer Institute, Thomas Jefferson University Philadelphia, PA 19107 1Department of Pathology, University of Pennsylvania Philadelphia, PA 19104 2Department of Pathology, University of Pittsburgh, Pittsburgh Cancer Institute Pittsburgh, PA 15213, USA
*To whom correspondence should be addressed
Received October 2, 1991. Revised February 19, 1992. Accepted February 19, 1992.
The Proliferating Cell Nuclear Antigen (PCNA) gene is a growth-regulated gene, whose expression is under the control of both transcriptlonal and post-transcriptional mechanisms. In previous work, it was shown that the 73 bp immediately upstream of the CAP site and intron 4 are major regulatory elements. We show here that intron 1 also plays a role in determining the levels of PCNA mRNA. Specifically, we show: 1) deletion of intron 1 increases the expression of PCNA mRNA in serum-deprived cells; 2) a 35 bp sequence in intron 1, containing a reverse CCAAT element specifically binds proteins from nuclear extracts; 3) this intron 1 sequence inhibits the expression of a co-tranfected human PCNA gene in transient expression assays suggesting that it competes for positive transcription factors; 4) mutations in the CCAAT region of the 35bp intron 1 probe abrogate both its protein-binding capacity and its ability to inhibit the expression of a co-transfected wt PCNA gene; and 5) the CCAAT region of human intron 1 is highly conserved in the mouse gene. We conclude that the reverse CCAAT region of intron 1 is a negative regulatory element of PCNA gene expression, and hypothesize that its inhibitory effect is abolished when certain protein(s) bind to it and that inhibition is restored if these proteins are competed out by an homologous sequence.
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