These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A regulatory element within a coding exon modulates keratin 18 gene expression in transgenic mice.
    Author: Neznanov N, Umezawa A, Oshima RG.
    Journal: J Biol Chem; 1997 Oct 31; 272(44):27549-57. PubMed ID: 9346889.
    Abstract:
    Multiple tissue-specific, DNase-hypersensitive sites are correlated with known or potential regulatory regions of the human keratin 18 (K18) gene. One of these sites is found within exon 6, close to a potential AP-1 binding site. Footprint analysis confirmed that this site is capable of binding c-Jun and c-Fos in vitro. However, exon 6 can stimulate expression of a reporter gene driven by the K18 proximal promoter independent of AP-1 in F9 cells and additionally modulates AP-1 responsiveness when in combination with an intron enhancer. Analysis in transgenic mice and by transient transfections of mutant forms of the K18 gene showed that exon 6 contributes to the expression of the K18 gene. However, substitution of part of exon 6 with the corresponding part of the keratin 19 gene which lacks an AP-1 site decreased but did not destroy the regulatory activity of the exon. Furthermore, this mutation did not alter either the tissue specificity or the position-independent and copy number-dependent behavior of the K18 gene. In contrast, a frameshift mutation within exon 6 dramatically decreased the expression of the gene. K18 RNA expression from the frameshift mutation was less than 10% of the wild type K18 transgene. This decline in expression was the result of a combination of decreased stability of mutant K18 RNA and the creation of a negative regulatory element that can interact with the first intron regulatory elements and actively suppress K18 expression. These results demonstrate that a protein-coding portion of the K18 gene also has a regulatory function.
    [Abstract] [Full Text] [Related] [New Search]