A nucleoprotein complex containing CCAAT/enhancer-binding protein beta interacts with an insulin response sequence in the insulin-like growth factor-binding protein-1 gene and contributes to insulin-regulated gene expression

Highly related insulin response sequences (IRSs) mediate effects of insulin on the expression of multiple genes in the liver, including insulin-like growth factor binding protein-1 (IGFBP-1) and phosphoenolpyruvate carboxykinase (PEPCK). Gel shift studies reveal that oligonucleotide probes containing an IRS from the IGFBP-1 or PEPCK gene form a similar complex with hepatic nuclear proteins. Unlabeled competitors containing the IGFBP-1 or PEPCK IRS or a binding site for C/EBP proteins inhibit the formation of this complex. Antibody against C/EBPbeta (but not other C/EBP proteins) supershifts this complex, and Western blotting of affinity purified proteins confirms that C/EBPbeta is present in this complex. Studies with affinity purified and recombinant protein indicate that C/EBPbeta does not interact directly with the IRS, but that other factors are required. Gel shift assays and reporter gene studies with constructs containing point mutations within the IRS reveal that the ability to interact with factors required for the formation of this complex correlates well with the ability of insulin to regulate promoter activity via this IRS (r = 0.849, p < 0.01). Replacing the IRS in reporter gene constructs with a C/EBP-binding site (but not an HNF-3/forkhead site or cAMP response element) maintains the effect of insulin on promoter activity. Together, these findings indicate that a nucleoprotein complex containing C/EBPbeta interacts with IRSs from the IGFBP-1 and PEPCK genes in a sequence-specific fashion and may contribute to the ability of insulin to regulate gene expression.     

子宫内膜蜕膜化的特征及其调节因素

子宫内膜向蜕膜的转化是正常着床和妊娠的一个重要特征,对于胚泡着床是必不可少的。在蜕膜化过程中,子宫内膜基质细胞在形态和生理等方面都发生了很大的变化。蜕膜化过程受多种因素的调节,包括cAMP、胰岛素样生长因子结合蛋白-1(IGFBP-1)、自然杀伤细胞、同源盒基因-10(HOXA10)、激活素等。但对蜕膜化的机制及调节等仍不清楚。     

Secretory proteins and growth factors of the baboon (Papio anubis) uterus: potential roles in pregnancy.

The primate endometrium undergoes distinct morphological changes during the menstrual cycle. These alterations are regulated by the steroid hormones, estrogen and progesterone. Several lines of evidence suggest that some of these hormonally induced changes may be modulated by growth factors. Our studies have focused on characterizing the secretory activity of the uterine endometrium associated with these hormonally regulated morphological changes during the menstrual cycle and pregnancy in the baboon. Additionally, we have also attempted to study the regulation of specific growth factors and their receptors. In this review we present evidence to indicate that growth factor receptors for insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF), and secretory proteins, insulin-like growth factor binding protein-1 (IGFBP-1) and retinol binding protein (RBP), which are present in the glandular epithelium during the menstrual cycle, undergo cell-specific changes in gene expression at the implantation site during pregnancy. We postulate that these alterations in growth factor receptor and secretory protein expression are conceptus modulated and may play important regulatory roles during trophoblast invasion and decidualization.     

HOXA10直接调控人子宫内膜间质细胞中p/CAF启动子的活性

目的：筛选与鉴定转录因子同源框蛋白（HOX）A10下游靶基因。方法：用Ad-HOXA10重组腺病毒感染人子宫内膜间质细胞,通过染色体免疫共沉淀（ChIP）方法,筛选HOXA10的下游靶基因;采用萤光素酶报告基因实验结合腺病毒介导的HOXA10过表达和小干扰RNA介导的基因沉默实验,分析HOXA10对下游靶基因的转录调控作用。结果：ChIP-PCR筛选并鉴定p/CAF（p300/CBP相关因子）为HOXA10直接作用的靶基因;过表达HOXA10抑制p/CAF启动子活性达60%;基因沉默内源性HOXA10的表达可以激活p/CAF启动子活性超过2倍以上。结论：p/CAF是HOXA10新的靶基因,HOXA10可能通过调节p/CAF的表达来调控子宫内膜的发育。