J Biol Chem, Vol. 273, Issue 41, 26534-26542, October 9, 1998
A Regulatory Element of the Human Keratin 18 Gene with
AP-1-dependent Promoter Activity
Katherine
Rhodes and
Robert G.
Oshima
From The Burnham Institute, La Jolla, California 92037
The human keratin 18 (K18) gene is expressed in a
restricted but diverse subset of differentiated epithelial tissues and
carcinomas. The 10-kilobase pair K18 gene contains all of the genetic
information necessary for tissue-specific, copy
number-dependent and integration site-independent
expression in transgenic mice. We identified a 100-base pair regulatory
element that activates the K18 proximal promoter in the presence of the
previously identified first intron enhancer. Deletion of the element
greatly diminished K18 expression. This regulatory element also has
cryptic, AP-1-dependent promoter activity in the absence of
the normal promoter, which results in 10-40-fold higher levels of K18
RNA expression in transgenic mice. The high activity of this cryptic
promoter is dependent upon the first intron enhancer. These experiments
define interactive regulatory regions of the K18 gene that modulate
expression in diverse epithelial cell types and identify an unusual
regulatory element with promoter activity that may be useful for high
level heterologous gene expression in transgenic animals.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.