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Stochastic modeling of eukaryotic transcription at the single nucleotide levelVashishtha, Saurabh January 2011 (has links)
DNA is the genetic material of a cell and is copied in the form of pre-mRNA through
transcription in eukaryotes. RNA polymerase II is responsible for the transcription of all
genes that express proteins. Transcription is a significant source of the stochasticity in
gene expression. In this thesis, I discuss the development of a biochemically detailed
model of eukaryotic transcription, which includes pre-initiation complex (PIC) assembly,
abortive initiation, promoter-proximal pausing and termination as the points that can be
slow steps for transcription. The stochastic properties of this model are studied in detail
by stochastic simulations with some preliminary mathematical analysis. The results of
this model suggest that PIC assembly can play the most significant role in affecting the
transcription dynamics. In addition, promoter-proximal pausing has been identified as a
potential noise regulatory step in eukaryotic transcription. These results show excellent
agreement with many experimental studies. / x, 107 leaves : ill. ; 29 cm
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