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Genomic analyses of transcription elongation factors and intragenic transcription

Authors: Chuang, James;

Genomic analyses of transcription elongation factors and intragenic transcription

Abstract

Transcription of protein-coding genes in eukaryotic cells is carried out by the protein complex RNA polymerase II. During the elongation phase of transcription, RNA polymerase II associates with transcription elongation factors which modulate the activity of the transcription complex and are needed to carry out co-transcriptional processes. Chapters 2 and 3 of this dissertation describe studies of Spt6 and Spt5, two conserved transcription elongation factors. Spt6 is a transcription elongation factor thought to replace nucleosomes in the wake of transcription. Saccharomyces cerevisiae spt6 mutants express elevated levels of intragenic transcripts, transcripts appearing to initiate from within gene bodies. We applied high resolution genomic assays of transcription initiation to an spt6-1004 mutant, allowing us to catalog the full extent of intragenic transcription in spt6-1004 and show for the first time on a genome-wide scale that the intragenic transcripts observed in spt6-1004 are largely explained by new transcription initiation. We also assayed chromatin structure genome-wide in spt6-1004, finding a global depletion and disordering of nucleosomes. In addition to increased intragenic transcription in spt6-1004, our results also reveal an unexpected decrease in expression from most canonical genic promoters. Comparing intragenic and genic promoters, we find that intragenic promoters share some features with genic promoters. Altogether, we propose that the transcriptional changes in spt6-1004 are explained by a competition for transcription initiation factors between genic and intragenic promoters, which is made possible by a global decrease in nucleosome protection of the genome. Spt5 is another transcription elongation factor, important for the processivity of the transcription complex and many transcription-related processes. To study the requirement for Spt5 in vivo, we applied multiple genomic assays to Schizosaccharomyces pombe cells depleted of Spt5. Our results reveal an accumulation of RNA polymerase ...

Country
United States
Related Organizations
Keywords

570, Bioinformatics, 610

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
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