Abdurahman Anwar, Ga Yuling, Ma Xuehai
Xinjiang Key Laboratory of Mental Development and Learning Science, School of Psychology, Xinjiang Normal University, Urumqi, Xinjiang, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Front Cell Dev Biol. 2025 Jul 1;13:1623135. doi: 10.3389/fcell.2025.1623135. eCollection 2025.
BMPR1B, a type I receptor in the BMP/Smad signaling pathway, was the first major gene identified in sheep () to regulate key reproductive traits such as ovulation rate (OR) and litter size (LS). Despite its critical role in reproductive performance, the transcriptional regulatory mechanisms governing ovine BMPR1B expression remain poorly understood. This study identified the promoter region of the BMPR1B gene and revealed that transcription factor ELK1 regulates its transcriptional activity. Luciferase reporter assays identified the region from -438 bp to -208 bp relative to the essential promoter of the BMPR1B gene as a critical regulatory element. Notably, candidate ELK1-binding elements (EBS) were detected in this promoter region. Interestingly, ELK1 significantly enhances BMPR1B transcriptional activity by binding to specific sites in the promoter region. Further analysis in ovine granulosa cells showed that ELK1 modulates BMPR1B expression and influences granulosa cell apoptosis through the BMPR1B signaling pathway. These findings provide new key targets and mechanistic insights into the molecular regulatory network of ovarin granulosa cell apoptosis, advancing our understanding of reproductive biology in sheep.
骨形态发生蛋白受体1B（BMPR1B）是骨形态发生蛋白（BMP）/Smad信号通路中的I型受体，是在绵羊中鉴定出的首个调控排卵率（OR）和产仔数（LS）等关键繁殖性状的主要基因。尽管其在繁殖性能中起关键作用，但调控绵羊BMPR1B表达的转录调控机制仍知之甚少。本研究鉴定了BMPR1B基因的启动子区域，并揭示转录因子ELK1调控其转录活性。荧光素酶报告基因检测确定，相对于BMPR1B基因基本启动子，-438 bp至-208 bp区域是关键调控元件。值得注意的是，在该启动子区域检测到候选ELK1结合元件（EBS）。有趣的是，ELK1通过与启动子区域的特定位点结合，显著增强BMPR1B转录活性。在绵羊颗粒细胞中的进一步分析表明，ELK1通过BMPR1B信号通路调节BMPR1B表达并影响颗粒细胞凋亡。这些发现为绵羊卵巢颗粒细胞凋亡的分子调控网络提供了新的关键靶点和机制见解，增进了我们对绵羊生殖生物学的理解。
