During oocyte growth, transcription is required to create RNA and protein reserves to achieve maternal competence. During this period, the general transcription factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (TBP2 or TRF3), which is essential for RNA polymerase II transcription. We show that in oocytes TBPL2 does not assemble into a canonical TFIID complex. Our transcript analyses demonstrate that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA survey genes, as well as specific endogenous retroviral elements. Transcription start site (TSS) mapping indicates that TBPL2 has a strong preference for TATA-like motif in core promoters driving sharp TSS selection, in contrast with canonical TBP/TFIID-driven TATA-less promoters that have broader TSS architecture. Thus, we show a role for the TBPL2/TFIIA complex in the establishment of the oocyte transcriptome by using a specific TSS recognition code.

The first steps of oocyte development from primordial follicle are characterised by a 1 growth phase, when unique RNA and protein reserves are created to achieve oocyte 2 competence. During this growth, oocytes do not divide and the general transcription 3 factor TATA binding protein (TBP) is replaced by its paralogue, TBPL2 (also called TBP2 4 or TRF3), which is essential for RNA polymerase II transcription (Pol II) 1,2 . However, 5 the composition and function of transcription machinery and the regulatory mechanisms 6 mediating Pol II transcription during this developmental stage remain unknown. In 7 somatic cells, the general transcription factor TFIID, which contains TBP and 13 TBP-8 associated factors, is the first to bind gene promoters to nucleate Pol II transcription 9 initiation 3 . Here, we show that in oocytes TBPL2 does not assemble into a canonical TFIID 10 complex, while it stably associates with TFIIA via distinct TFIIA interactions when 11 compared to TBP. Our transcript analyses in wild type and Tbpl2 -/oocytes demonstrates 12 that TBPL2 mediates transcription of oocyte-expressed genes, including mRNA 13 destabilisation factors genes, as well as specific endogenous retroviral elements (ERVs). 14 Transcription start site (TSS) mapping from wild-type and Tbpl2 -/growing oocytes 15demonstrates that TBPL2 has a strong preference for TATA-like motif in gene core 16 promoters driving specific sharp TSS selection. This is in marked contrast with 17 TBP/TFIID-driven TATA-less gene promoters in preceding stages that have broad TSS 18 architecture. We anticipate that our findings describing oocyte-specific transcription 19 regulation will help to understand the mechanisms associated with primary ovarian 20 insufficiency, which constitutes a frequent cause of infertility among women. 21 22