BN seminar Anders Sejr Hansen (Associate Professor Department of Biological Engineering, MIT)

Abstract:
3D genome structure regulates gene expression by regulating the interactions between enhancers and promoters. CTCF and loop-extruding cohesins fold the genome into loops and domains known as Topologically Associating Domains (TADs). However, whether these domains were stable or dynamic was not clear. First, we will briefly discuss our recent work live-imaging work quantifying the dynamics of CTCF- and cohesin-mediated chromatin looping and the implications of our finding that these loops are both highly dynamic (~10-30 min median lifetime) and rare (~3%-6.5% looped fraction).

Second, motivated by understanding the degree of selectivity for interactions between enhancers and promoters, we will discuss more recent work and unpublished focused on quantifying the interactions between enhancers and promoters (E-P). Specifically, Hi-C has poor sensitivity and depth for capturing E-P interactions. To overcome this limitation, we have developed Region-Capture Micro-C (RCMC) to generate the deepest 3D genome structure maps reported so far. With RCMC, we find extensive multi-way looping interactions between enhancers and promoters that are largely independent of loop extrusion. Instead, our results suggest that E-P interactions form through a compartmentalization mechanism and we therefore refer to these fine-scale interactions as “microcompartments”. We will also discuss recent unpublished work on how E-P interactions dynamically form upon mitotic exit and recent applications of machine learning to impute 3D genome structure. Finally, we will integrate these observations to present our current view for how the cell regulates which enhancers interact with and activate which genes.

Short bio:
Anders obtained his undergraduate and Master’s degree in Chemistry at Oxford University in 2010. He received his PhD in Chemistry and Chemical Biology from Harvard University in 2015, where he worked with Erin O’Shea and applied systems biology approaches to understand how cells can encode and transmit information in the dynamics of transcription factor activation. For his post-doc at UC Berkeley with Robert Tjian and Xavier Darzacq, Anders developed new imaging approaches to track single proteins in living cells and applied these to understand the mechanisms of key architectural proteins involved in 3D genome organization.

Anders began his independent lab at MIT in 2020 where he is currently an Associate Professor of Biological Engineering. The Hansen lab is broadly interested in 3D genome structure and function, and develops new super-resolution and single-molecule imaging methods to track chromatin looping, transcription, and protein dynamics in living cells as well as new 3D genome structure mapping methods. Current application areas of interest include the dynamics of chromatin looping and transcription, how misfolding of the genome causes disease, the basic mechanisms of 3D genome folding, and synthetic 3D genome biology.

Anders has won several awards including an NIH Director’s New Innovator award (2020), a Pew-Stewart Scholar for Cancer Research award (2021), and an NSF CAREER award (2024).

Anders Sejr Hansen, PhD
Associate Professor
Department of Biological Engineering, MIT
Associate Member, Broad Institute of MIT and Harvard
Extramural Member, Koch Institute for Integrative Cancer Research