Biological Sciences Seminars

Long Range Gene Regulation: Design Principles of Epigenetic Silencing: Two stories of modeling in Molecular Biology

by Dr. Swagatam Mukhopadhayay (Cold Spring Harbor Laboratory, New York, USA)

Thursday, October 3, 2013 from to (Asia/Kolkata)
at Colaba Campus ( AG-66 )
Description
Long range gene regulation is common in Eukaryotes. Regulatory elements like enhancers and insulators, often acting in a non-specific and locus dependent manner, can influence the target promoters at a distance of upto 1 Mbp. How does such long-range regulation happen? Chromatin is organized in loop domains, either by insulator elements or nuclear tethering, and these loops are implicated in both efficient enhancement and insulation. I will discuss a biophysical model of chromatin, capable of discriminating various mechanisms of long-range gene regulation proposed in the literature, ultimately offering a unifying picture of chromatin organization. I will talk of using such biophysical model, to analyze Chromatin Conformation Capture data. 
   
The nucleation, spreading, inheritance and maintenance of epigenetic marks ubiquitous on chromatin, is pivotal to cell differentiation and epigenetic memory. A well studied system is the budding yeast Sir-mediated silencing. The design principles of the Sir system are being actively debated, I will present a minimal model based entirely on known biochemical interactions, explaining several apparently contradictory experimental observations. The model illuminates engineering design principles which may be applicable to other silencing systems. I will also present unpublished data from experiments inspired by such modeling efforts.