Final Project: Bharat Ravi – Regulation of transcription by G-quadruplexes

G-Quadruplexes (GQ) are nucleic acid super-secondary structures forming at G rich regions with a (G2+N1-5 )2+ motif. GQs consist of stacked quartets that are in turned formed by Hoogsteen hydrogen bonded Guanines, and are stabilized by potassium (and sodium) ions. GQs were initially discovered in telomeric sequences but later studies showed their enrichment in promoter and other geneic regions (Du et al., 2007; Lam et al., 2013). Their high enrichment in these regions of the genome suggests that they could play a role in gene regulation. However, most studies on quadruplexes have been done in-vitro especially with respect to their biophysical aspects. Even though GQs have been suggested to influence gene regulation, this possibility has not been thoroughly explored.

I explore the potential effects of GQs on transcription using mathematical models. I have used both deterministic model and stochastic model to study the transcription dynamics in the presence or absence of GQ. In both the models it has been assumed that GQs are downstream of the RNA polymerase binding site and four cases have been explored:

  1. No quadruplex
  2. Quadruplex in template strand
  3. Quadruplex in non-template strand
  4. Quadruplex in both the strands

Most parameters used in the model are adapted from the values reported by biophysical studies, while others have been assumed from guesses.

The models prove that G-quadruplexes can indeed regulate transcription. Future studies would include studying the effect of different parameters on the system and to perform experiments to validate the model.

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