Each cell of a multicellular organism contains identical linear genome sequence. To help understand how linear sequence results in the expression of specific genes and highly specialized functions in different cell types, the past two decades have seen an increased interest in mapping 3D genome architecture.
From the activity of enhancer in activating specific genes, to where in the nucleus are specific genomic regions localised, there is an increased awareness of how genome folding in 3D contributes to transcriptional regulation. Genome-wide methods for measuring chromatin folding are essential to properly understand the relationship between folding and transcription, yet different techniques have specific biases, and few can be easily applied to small numbers of specialized cells in complex tissues. In my presentation, I will discuss the application of Genome Architecture Mapping (GAM) in different cells of thejuvenile/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 found cell-type specific 3D chromatin structures that relate with patterns of gene expression at all genomic length scales, including extensive reorganization of topological domains and chromatin compartments. We discover the loss of TAD insulation, or "TAD melting", at long genes (>400kb) when they are highly transcribed, many of which are associated with neurodevelopmental disorders, such as autism spectrum disorders or schizophrenia. Overall, our work shows that the 3D organization of the genome is highly cell-type specific in terminally differentiated cells, and is an essential feature to better understand brain-specific mechanisms of gene regulation.
25 Jan | 12:00 | videoconf link