Identification of an Epithelial-Specific Enhancer Regulating ESX Expression

Authors

Richard M. Neve, Cancer Research Institute, University of California San Francisco, Box 0808, San Francisco, CA 94143-0808, USA
Hema Parmar, Cancer Research Institute, University of California San Francisco, Box 0808, San Francisco, CA 94143-0808, USA
Cliff Amend, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
Chira Chen, Cancer Research Institute, University of California San Francisco, Box 0808, San Francisco, CA 94143-0808, USA
Angie Rizzino, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA
Christopher C. Benz, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA

Date of this Version

2006

Comments

Published in Gene 367 (2006) 118–125.

Abstract

The Ets transcription factor, ESX, exhibits a unique pattern of epithelial-restricted expression and transactivates genes involved in epithelial differentiation and cancer. The aim of this study was to determine the underlying genetic basis for epithelial-specific expression of ESX. We have identified a 30bp ESX enhancer sequence (EES) approximately 3 kb upstream of the proximal promoter. This region displays enhancer activity in an epithelial-specific manner and deletion of this region abrogates ESX gene transcription. An EES binding protein complex (EBC) was identified through electrophoretic mobility shift assays whose degree of EES binding correlated well with endogenous ESX levels in epithelial cells and was regulated by epithelial differentiation. Understanding the regulation of this element will lend insight into mechanisms of epithelial differentiation and the etiology of breast cancer and may provide novel targets for cancer therapeutic intervention.