A conserved region in intron 1 negatively regulates the expression of the PCNA gene

Hansjuerg Alder, Mitsuo Yoshinouchi, Michael B. Prystowsky, Pierette Appasamy, Renato Baserga

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1769-1775
Number of pages7
JournalNucleic acids research
Volume20
Issue number7
DOIs
StatePublished - Apr 11 1992
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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