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TBPL2/TFIIA complex overhauls oocyte transcriptome during oocyte growth
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The first steps of oocyte development from primordial follicle are characterised by a growth phase, when unique RNA and protein reserves are created to achieve oocyte competence. During this growth, oocytes do not divide and the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (also called TBP2 or TRF3), which is essential for RNA polymerase II transcription (Pol II) 1,2 . However, the composition and function of transcription machinery and the regulatory mechanisms mediating Pol II transcription during this developmental stage remain unknown. In somatic cells, the general transcription factor TFIID, which contains TBP and 13 TBP-associated factors, is the first to bind gene promoters to nucleate Pol II transcription initiation 3 . Here, we show that in oocytes TBPL2 does not assemble into a canonical TFIID complex, while it stably associates with TFIIA via distinct TFIIA interactions when compared to TBP. Our transcript analyses in wild type and Tbpl2 -/- oocytes demonstrates that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA destabilisation factors genes, as well as specific endogenous retroviral elements (ERVs). Transcription start site (TSS) mapping from wild-type and Tbpl2 -/- growing oocytes demonstrates that TBPL2 has a strong preference for TATA-like motif in gene core promoters driving specific sharp TSS selection. This is in marked contrast with TBP/TFIID-driven TATA-less gene promoters in preceding stages that have broad TSS architecture. We anticipate that our findings describing oocyte-specific transcription regulation will help to understand the mechanisms associated with primary ovarian insufficiency, which constitutes a frequent cause of infertility among women. . The first steps of oocyte development from primordial follicle are characterised by a growth phase, when unique RNA and protein reserves are created to achieve oocyte competence. During this growth, oocytes do not divide and the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (also called TBP2 or TRF3), which is essential for RNA polymerase II transcription (Pol II) 1,2 . However, the composition and function of transcription machinery and the regulatory mechanisms mediating Pol II transcription during this developmental stage remain unknown. In somatic cells, the general transcription factor TFIID, which contains TBP and 13 TBP-associated factors, is the first to bind gene promoters to nucleate Pol II transcription initiation 3 . Here, we show that in oocytes TBPL2 does not assemble into a canonical TFIID complex, while it stably associates with TFIIA via distinct TFIIA interactions when compared to TBP. Our transcript analyses in wild type and Tbpl2 -/- oocytes demonstrates that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA destabilisation factors genes, as well as specific endogenous retroviral elements (ERVs). Transcription start site (TSS) mapping from wild-type and Tbpl2 -/- growing oocytes demonstrates that TBPL2 has a strong preference for TATA-like motif in gene core promoters driving specific sharp TSS selection. This is in marked contrast with TBP/TFIID-driven TATA-less gene promoters in preceding stages that have broad TSS architecture. We anticipate that our findings describing oocyte-specific transcription regulation will help to understand the mechanisms associated with primary ovarian insufficiency, which constitutes a frequent cause of infertility among women.
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