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Open AccessArticle

Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells

1
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
2
College of Animal Science and Technology, Xinjiang Agricultural University, Urumqi 830001, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2732; https://doi.org/10.3390/ijms20112732
Received: 30 April 2019 / Revised: 26 May 2019 / Accepted: 3 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue TGF-Beta Super Family Signaling 2.0)
BMPR1B is a type 1B receptor of the canonical bone morphogenetic protein (BMP)/Sma- and mad-related protein (Smad) signaling pathway and is well known as the first major gene associated with sheep prolificacy. However, little is known about the transcriptional regulation of the ovine BMPR1B gene. In this study, we identified the ovine BMPR1B gene promoter and demonstrated that its transcription was regulated by Smad4. In sheep ovarian follicles, three transcriptional variants of BMPR1B gene with distinct transcription start sites were identified using 5′ RACE assay while variants II and III were more strongly expressed. Luciferase assay showed that the region −405 to −200 nt is the PII promoter region of variant II. Interestingly, two putative Smad4-binding elements (SBEs) were detected in this region. Luciferase and ChIP assay revealed that Smad4 enhances PII promoter activity of the ovine BMPR1B gene by directly interacting with SBE1 motif. Furthermore, in the ovine granulosa cells, Smad4 regulated BMPRIB expression, and BMPRIB-mediated granulosa cells apoptosis. Overall, our findings not only characterized the 5’ regulatory region of the ovine BMPR1B gene, but also uncovered a feedback regulatory mechanism of the canonical BMP/Smad signaling pathway and provided an insight into the transcriptional regulation of BMPR1B gene and sheep prolificacy. View Full-Text
Keywords: sheep; BMPR1B; transcription factor; Smad4; granulosa cell apoptosis sheep; BMPR1B; transcription factor; Smad4; granulosa cell apoptosis
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MDPI and ACS Style

Abdurahman, A.; Du, X.; Yao, Y.; Sulaiman, Y.; Aniwashi, J.; Li, Q. Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells. Int. J. Mol. Sci. 2019, 20, 2732. https://doi.org/10.3390/ijms20112732

AMA Style

Abdurahman A, Du X, Yao Y, Sulaiman Y, Aniwashi J, Li Q. Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells. International Journal of Molecular Sciences. 2019; 20(11):2732. https://doi.org/10.3390/ijms20112732

Chicago/Turabian Style

Abdurahman, Anwar; Du, Xing; Yao, Yilong; Sulaiman, Yiming; Aniwashi, Jueken; Li, Qifa. 2019. "Smad4 Feedback Enhances BMPR1B Transcription in Ovine Granulosa Cells" Int. J. Mol. Sci. 20, no. 11: 2732. https://doi.org/10.3390/ijms20112732

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