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Transcription et "silencing" des gènes ribosomiques : étude du mode de transcription et de la régulation épigénétique des gènes codant les ARN ribosomiques
| Content Provider | Semantic Scholar |
|---|---|
| Author | Langlois-Charette, Frédéric |
| Copyright Year | 2011 |
| Abstract | Transcription of the genes encoding the ribosomal RNAs is essential to the synthesis of ribosomes, that are in turn required to make cellular protein. Thus, ribosomal RNA transcription is a prerequisite for most cellular functions. Despite this fundamental role, the mechanisms underlying ribosomal RNA synthesis are still poorly understood. My first aim was to characterize the role of the protein UBF in transcriptional regulation. UBF binds to the DNA of the ribosomal genes and forms a structure that has been called the Enhancesome. ERK phosphorylation of the HMGl-box domains provokes a change in the conformation of the Enhancesome and ERK signaling rapidly increases ribosomal transcription but does not change the number of polymerases that transcribe the ribosomal RNA genes. ERK phosphorylation of UBF allows passage of the transcribing RNA polymerase I, making UBF a growth regulated modulator of transcription elongation. On a different note, DNA méthylation is linked to epigenetic repression. We have shown that the loss of CpG méthylation leads to a partial activation of silenced genes but also to severe transcriptional and processing defects. I could show that an increased accessibility of the chromatin allows RNA polymerase II to bind and aberrantly to transcribe RNA on the rDNA locus. I further studied the genomic distribution of TTF-I, a transcription factor that shuttles between the nucleus and the ribosomal genes, and whose nucleolar import is regulated by the ARF tumor suppressor. Apart from its known binding sites on the ribosomal RNA genes, TTF-I was also found at several RNA polymerse II promoters throughout the genome. However its role at these sites remains unclear and will require further study. Finally, in order to study to distinguish events occurring on active and inactive ribosomal genes, I developped a sequential chromatin immunoprecipitation procedure. Preliminary results indicate that UBF preferentially targets actively transcribed rDNA regions and that these are devoid of histones. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://corpus.ulaval.ca/jspui/bitstream/20.500.11794/22819/1/28070.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
