Tissue-specific expression of the human alpha 1-antitrypsin gene is controlled by multiple cis-regulatory elements.
AUTOR(ES)
Shen, R F
RESUMO
Human alpha 1-antitrypsin (AAT) is expressed in the liver, and a 318 bp fragment immediately flanking the CAP site of the gene was found to be sufficient to drive the expression of a reporter gene (CAT) specifically in hepatoma cells. The enhancing activity however, was orientation-dependent. The DNA fragment was separated into a distal region and a proximal region. A "core enhancer" sequence GTGGTTTC is present within the distal region and is capable of activity enhancement in both orientations when complemented by the proximal region in the sense orientation. The results strongly suggest that there are multiple cis-acting elements in the human AAT gene that confer cell specificity for its expression. Nuclear proteins prepared from the hepatoma cells bound specifically to the proximal region in a band-shifting assay that was resistant to competition by the globin promoter DNA. Foot-printing analysis showed a protected domain within the proximal region that contains a nearly perfect palindromic sequence TGGTTAATATTCACCA, which may be important in the regulation of AAT expression in the liver.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=306367Documentos Relacionados
- Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene.
- The human alpha-1-antitrypsin gene is efficiently expressed from two tissue-specific promotors in transgenic mice.
- Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements.
- Tissue-specific control elements of the Thy-1 gene.
- Functional characterization of the cis-regulatory elements of the rat ribophorin I gene.