Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip.
BACKGROUND
UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells.


RESULTS
UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional chromatin immunoprecipitation and quantitative real time PCR were used to validate promoter binding and expression changes. Small interfering RNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that a downstream target of the epidermal growth factor receptor, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest.


CONCLUSIONS
Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV stimulation and led to the identification of downstream targets of Egr1, which mediate epidermal growth factor receptor function.
Arora
Shilpi
S
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA. sarora@tgen.org
Wang
Yipeng
Y
Jia
Zhenyu
Z
Vardar-Sengul
Saynur
S
Munawar
Ayla
A
Doctor
Kutbuddin S
KS
Birrer
Michael
M
McClelland
Michael
M
Adamson
Eileen
E
Mercola
Dan
D
D017209:Apoptosis / Q000528:radiation effects; D002461:Cell Line, Transformed; D047369:Chromatin Immunoprecipitation; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1