Cell-type specialization in the brain is encoded by specific long-range chromatin topologies
by Prof. Dr. Ana Pombo of the Max-Delbrück Centre for Molecular Medicine (Berlin, Germany)
Terminally differentiated cells sustain cascades of gene activation and repression to execute highly specialized functions, while retaining homeostatic control during the lifetime of an organism. We developed the application of Genome Architecture Mapping in combination with immunoselection (immunoGAM) to study long-range chromatin folding in specialized brain cells, without disturbing their native tissue environment. We applied immunoGAM in three specialized cell types from the juvenile/adult murine brain: dopaminergic neurons (DNs) from the midbrain, pyramidal glutamatergic neurons (PGNs) from the hippocampus, and oligodendrocyte lineage cells (OLGs) from the cortex. We discover the loss of TAD insulation, or ‘TAD melting’, at long genes (>400kb) when they are highly transcribed. We find many regulatory regions within neuron-specific pairwise contacts, which contain complex combinations of binding sites for neuronal transcription factors, and which connect neuron-specific expressed genes associated with specialized neuronal functions, such synaptic plasticity and memory. Our work shows that the 3D organization of the genome is highly cell-type specific in terminally differentiated cells of the brain, and essential to better understand brain-specific mechanisms of gene regulation.
Speaker invited by CRG and colloquium moderated by Luciano di Croce.
The colloquium is part of the BIST Master of Research curriculum but is also open and free for anyone interested in participating.
Join the Zoom Session on Monday Sept 28, at 5:00PM
Meeting ID: 846 479 2958
Password: MMRES
The session will be hosted through Zoom online conference application. If you have not used this platform previously, you will be prompted to download the software to access the meeting (the process is automatic and does not require more than one minute).
Next colloquia will be:
October 5 – Prof. Sarah-Maria Fendt of theKatholieke Universiteit Leuven
October 19 – Prof. Dr. Dr. hc. Viola Vogel of the ETH Zürich
October 21 – Prof. Fabrizio d’Adda of the IFOM
October 26 – Prof. Raffaella Buonsanti of the EPFL
November 2 – Prof. Dr. Oscar Franco of the Institute of Social and Preventive Medicine
November 9 – Georgia Theano Papadakis of Stanford University
November 16 – Rogério Rosenfeld of Universidade Estadual Paulista