Transcription factor BRCA1 is associated with BMPR1B transcriptional activity in sheep ovarian granulosa cells

TL;DR

This study shows that the BRCA1 protein regulates the BMPR1B gene in sheep ovarian cells, which affects reproduction and cell survival.

Contribution

The study identifies BRCA1 as a regulator of BMPR1B transcription and its role in granulosa cell apoptosis in sheep.

Findings

The BMPR1B promoter region has two BRCA1 binding sites, with BBS2 being more influential in transcriptional activity.

BRCA1 expression correlates with BMPR1B expression and reduces granulosa cell apoptosis in sheep.

Luciferase assays confirmed the promoter activity of the BMPR1B gene in sheep.

Abstract

BMPR1B is a well-characterized major gene associated with prolificacy in sheep. The FecB mutation in this gene promotes accelerated follicular development and increases ovulation rate, thereby enhancing litter size. Although BMPR1B plays a crucial role in reproduction, the regulatory mechanisms of its expression in sheep tissues are not yet fully understood. This study identified the promoter region of the BMPR1B gene and provided evidence that its transcriptional activity is associated with regulation by the transcription factor BRCA1. Luciferase reporter assays showed that the P1 fragment containing the BMPR1B promoter region had gene expression-driving activity; importantly, two BRCA1 binding sites (BBS) were identified within this promoter region. Subsequent experimental results suggest that BRCA1’s effect on BMPR1B transcriptional activity may be achieved through BBS2 rather than BBS1. Further studies in sheep ovarian granulosa cells (GCs) have shown that BRCA1 expression is correlated with BMPR1B expression and is linked to reduced granulosa cell apoptosis. Collectively, these findings provide a basis for the BRCA1-BMPR1B regulatory axis and offer new insights into the molecular framework influencing ovarian granulosa cell apoptosis in sheep.

Figures