The yeast HMGB yeast protein Hmo1 displays altered genome-wide binding due to a stress response following topoisomerase depletion

Diplôme Master The yeast HMGB yeast protein Hmo1 displays altered genome-wide binding due to a stress response following topoisomerase depletion eng 2018 author Rueda Mejia Maria Paula 851670 director Shore David M. 102587 director Albert Benjamin 808748 Transcription initiation requires a series of sequential events, nucleosomes must be displaced from the promoter region and the proteins that form the preinitiation complex must be recruited, starting with TBP and ending with the RNA polymerase. Then, for elongation, the DNA double helix must be separated to access the nucleotide information, due to its intertwined nature this produces positive supercoiling in front of the polymerase and negative behind. Topoisomerases are the enzymes that perform transient breaks to DNA strands to release supercoiling. Some HMGB proteins also seem to be involved in transcription, this family of small and abundant proteins includes Hmo1 and Nhp6 in yeast, they bind DNA without sequence specificity and seem to be preferentially recruited to distorted DNA configurations. These two proteins are enriched in highly transcribed genes, both in RP genes and Hmo1 at rDNA. There is a feedback regulation between transcription, torsional tension and topoisomerases. However, the mechanisms by which topoisomerase activities modulate transcription are not well understood. In this work, we studied topoisomerase function by the degradation of these proteins with the auxin degron system. The effect of this inhibition on the binding profiles of the RNA polymerase II, TBP, NHP6 and Hmo1 was measured by ChIP-seq. Our evidence shows TBP recruitment could be sensitive to helical tension. Hmo1 presented a strong shift of binding sites, with new recruitment at promoters of genes related to environmental stress response. Further investigation into the causes of Hmo1 recruitment shows this alteration depends of a unique change of its nucleolar localization and the activation of stress response pathways. This evidence led to the postulation of Hmo1 as a factor related to stress response that protects the nucleosome-depleted sections of DNA. Topoisomerase Hmo1 HMGB Transcription Dewey 570 43 Département de biologie moléculaire 161 false 813 Groupe Shore 28ada376-e0a7-4046-9ca4-d81fd51defbc Master thesis Restricted Rueda_Mariamasterthesis12.pdf 5953608 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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The yeast HMGB yeast protein Hmo1 displays altered genome-wide binding due to a stress response following topoisomerase depletion				2018	114	3

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Rueda Mejia, Maria Paula