Seo Bong-Jong, Son Ji Won, Kim Hye-Ryun, Hong Seok-Ho, Song Haengseok
Department of Biomedical Science, CHA University, Seoul 135-081, Republic of Korea.
Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Dev Reprod. 2014 Mar;18(1):1-11. doi: 10.12717/DR.2014.18.1.001.
Early growth response 1 (Egr1) is a zinc-finger transcription factor to direct second-wave gene expression leading to cell growth, differentiation and/or apoptosis. While it is well-known that Egr1 controls transcription of an array of targets in various cell types, downstream target gene(s) whose transcription is regulated by Egr1 in the uterus has not been identified yet. Thus, we have tried to identify a list of potential target genes of Egr1 in the uterus by performing multi-step in silico promoter analyses. Analyses of mRNA microarray data provided a cohort of genes (102 genes) which were differentially expressed (DEGs) in the uterus between Egr1(+/+) and Egr1(-/-) mice. In mice, the frequency of putative EGR1 binding sites (EBS) in the promoter of DEGs is significantly higher than that of randomly selected non-DEGs, although it is not correlated with expression levels of DEGs. Furthermore, EBS are considerably enriched within -500 bp of DEG's promoters. Comparative analyses for EBS of DEGs with the promoters of other species provided power to distinguish DEGs with higher probability as EGR1 direct target genes. Eleven EBS in the promoters of 9 genes among analyzed DEGs are conserved between various species including human. In conclusion, this study provides evidence that analyses of mRNA expression profiles followed by two-step in silico analyses could provide a list of putative Egr1 direct target genes in the uterus where any known direct target genes are yet reported for further functional studies.
早期生长反应1（Egr1）是一种锌指转录因子，可指导第二波基因表达，从而导致细胞生长、分化和/或凋亡。虽然众所周知Egr1可控制多种细胞类型中一系列靶标的转录，但Egr1在子宫中调控转录的下游靶基因尚未确定。因此，我们试图通过多步骤的计算机启动子分析来确定子宫中Egr1的潜在靶基因列表。对mRNA微阵列数据的分析提供了一组基因（102个基因），这些基因在Egr1（+/+）和Egr1（-/-）小鼠的子宫中差异表达（DEGs）。在小鼠中，DEGs启动子中假定的EGR1结合位点（EBS）的频率显著高于随机选择的非DEGs，尽管它与DEGs的表达水平无关。此外，EBS在DEGs启动子的-500 bp范围内大量富集。对DEGs的EBS与其他物种启动子的比较分析有助于更大概率地区分DEGs作为EGR1直接靶基因。在分析的DEGs中，9个基因启动子中的11个EBS在包括人类在内的各种物种之间是保守的。总之，本研究提供了证据，即通过两步计算机分析对mRNA表达谱进行分析，可以提供子宫中假定的Egr1直接靶基因列表，而目前尚未报道任何已知的直接靶基因，以供进一步的功能研究。
