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.
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Meeting ID: 846 479 2958
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