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Identification of Egr1 direct target genes in the uterus with in silico analyses
- 언어ENG
- URLhttps://db.koreascholar.com/Article/Detail/354993
Early growth response 1 (Egr1) is an immediate early response gene which is induced by various external stimuli and acts as transcription factor to direct second-wave gene expression leading to cell growth, differentiation and/or apoptosis. It is well known that Egr1 regulates transcription of a cluster of genes in cancers and luteinizing hormone (LH) beta subunit in the pituitary. In addition to function of Egr1 in cancers and pituitary, we recently showed that Egr1 acts as a local master regulator to mediate estrogenic actions in the uterus. However, regulatory mechanism by which Egr1 directs transcription of its downstream target genes in the uterus remains to be yet explored. Thus, we have tried to identify direct target genes of Egr1 in the uterus by analyzing mRNA microarray data sets followed by in silico promoter analyses with chromatin immunoprecipitation (CHIP). mRNA expression profiles of Egr1(－/－) uteri and Egr1(－/－) ovaries were compared to those of wildtype mice to provide a potential list of direct target genes of Egr1 in the uterus. Whereas Egr1 is rapidly and transiently induced in the ovary and the uterus by external stimuli, LH and estrogen, respectively with a similar manner, a list of differentially expressed genes between Egr1(+/+) and Egr1(－/－) mice were barely overlapped between these two datasets. This result suggests that the transcriptional network of Egr1 in the uterus is quite different from that in the ovary. The list of differentially expressed genes in Egr1(－/－) uterus was enriched by RT-PCR. In silico analyses with MatInspector provided evidence that Egr1 binding sites are relatively enriched in －500 bp promoter regions of genes in the list. CHIP assays for Egr1 antibody with uterine tissues 2 h after estrogen treatment reinforced the possibility that genes identified in this study such as Gadd45g and Lbh could be directly regulated by Egr1 in uterine context. Collectively, we show that bioinformatic analyses of expression profiles with in silico analyses could be a useful tool to enrich potential candidates of direct target genes of transcription factors.
