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Condensed Matter / Biophysics Seminar – Sumitabha Brahmachari, Rice University
Deciphering the role of the physicochemical properties of DNA in governing biological function
Genomic DNA contains the code of cellular life. Understanding the principles regulating transcription of the genetic code is imperative to comprehend biological functions like stress response, disease progression, and cellular differentiation. However, more than just learning the sequence is often required to decode these principles. Appreciating that the chromosomes are folded polymers with well-defined chemical or epigenetic identities and proteins are locally-acting nano-machines that apply forces and torques and catalyze chemical reactions is crucial to unveiling the regulatory principles. In this talk, I will discuss a model for active genic segments that uncovers the role of mechanical constraints in regulating transcription. We propose distinct regimes of DNA twist-mediated coupling between various transcription machinery components that explain novel experimental signatures and make testable predictions. I will conclude with our ongoing efforts toward an integrated picture where an interplay between transcription, epigenetic characteristics, and the three-dimensional architecture of the genome regulate phenotypical characteristics like epigenetic stability and cell fate.