Centre d'Immunologie Marseille-Luminy and Inflammation Biology, King’s College London, UK
Contact IRCM : Laurent LeCam
"DDR" lab, IPBS - CNRS/Université de Toulouse
ICM, Hopital Pitié Salpétrière, Paris
IGBMC, Illkirch, France
The seminar in brief:
Transcription mediated by RNA polymerase II (RNA Pol II) is responsible for the expression of protein-coding genes and many non-coding RNAs in all cells of the body. Disruption of RNA Pol II activity is thus associated with many diseases. Understanding the mechanisms that control transcription is therefore of fundamental but also medical interest. Our laboratory focuses on the protein complexes that are involved in RNA Pol II transcription initiation, the first step of the transcriptional cycle, in particular on the general transcription factor (GTF) TFIID. The TFIID complex is the first GTF to interact with DNA by recognizing the promoter and allows the nucleation of the pre-initiation transcription complex (PIC). TFIID is composed of TBP (TATA-binding protein) and 13 TAFs (TBP-associated factors) in higher eukaryotes.
This somewhat simplistic view has been challenged in metazoans, because the composition of TFIID is in fact more complex. Indeed, i) some subunits are not necessarily required in certain cellular contexts, ii) some TAFs have paralogs that are associated with developmental programs and that can be integrated into TFIID and iii) there are TBP-like proteins associated with gamete differentiation but it is not clear whether these TBP-like proteins are capable of integrating a TFIID complex. All these data indicate that there is potential diversity in the mechanisms of promoter recognition and transcription initiation and that this step can be considered as a new level of regulation of gene expression.
Our aim is to analyze the functional diversity of the protein complexes that recognize the promoters and initiate the formation of the PIC. We have identified a unique TFIID-independent basal transcription machinery during oocyte growth and analyzed the effects of deletion of genes encoding certain TAFs on TFIID composition and Pol II transcription during murine development and in embryonic stem cells.
INSERM U1239 (NorDic) IRIB, Université de Rouen-Normandie, Rouen