Abstract:
The mechanism underlying the initiation of parturition remains unclear. Cyclooxygenase 2 and prostaglandins in decidual membrane tissue play an important role in the \"parturition cascade.\" With the advancement of gestation, the expression of the transcriptional suppressor B lymphocyte-induced maturation protein 1 in the decidual membrane gradually decreases. Through chromatin immunoprecipitation sequencing, we found that B lymphocyte-induced maturation protein 1 has a binding site in the distal intergenic of PTGS2(COX2). Tripartite motif-containing protein 66 is a chromatin-binding protein that usually performs transcriptional regulatory functions by \"reading\" histone modification sites in chromatin. In this study, tripartite motif-containing protein 66 exhibits the same trend of expression as B lymphocyte-induced maturation protein 1 in the decidua during gestation. Moreover, the co-immunoprecipitation assay revealed that tripartite motif-containing protein 66 combined with B lymphocyte-induced maturation protein 1. This finding indicated that tripartite motif-containing protein 66 formed a transcription complex with B lymphocyte-induced maturation protein 1, which coregulated the expression of COX2. In animal experiments, we injected si-Blimp1 adenoviruses (si-Blimp1), Blimp1 overexpression plasmid (Blimp1-OE), and Trim66 overexpression plasmid (Trim66-OE) through the tail vein of mice. The results showed that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 affected the initiation of parturition in mice. Therefore, the present evidence suggests that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 partially participate in the initiation of labor, which may provide a new perspective for exploring the mechanism of term labor.
摘要:
开始分娩的潜在机制尚不清楚。蜕膜组织中的环氧合酶2(COX2)和前列腺素(PGs)在“分娩级联”中起重要作用。随着妊娠的推进,蜕膜中转录抑制因子B淋巴细胞诱导成熟蛋白1(BLIMP1)的表达逐渐降低。通过染色质免疫沉淀测序,我们发现BLIMP1在PTGS2(COX2)的远端基因间有一个结合位点。含三方基序的蛋白66(TRIM66)是一种染色质结合蛋白,通常通过“读取”染色质中的组蛋白修饰位点来执行转录调节功能。在这项研究中,TRIM66在妊娠期间在蜕膜中表现出与BLIMP1相同的表达趋势。此外,免疫共沉淀试验显示TRIM66与BLIMP1联用。这一发现表明TRIM66与BLIMP1形成转录复合物,其共同调节COX2的表达。在动物实验中,我们注射了si-Blimp1腺病毒,Blimp1过表达质粒(Blimp1-OE)和Trim66过表达质粒(Trim66-OE)经由小鼠尾静脉。结果表明,BLIMP1和TRIM66影响小鼠的分娩开始。因此,目前的证据表明,BLIMP1和TRIM66部分参与了分娩的启动,这可能为探索长期劳动机制提供新的视角。