Apr 2, 2020

Cell-type specialization in the brain is encoded by specific long-range chromatin topologies

BioRxiv : the Preprint Server for Biology
W. Winick-NgAna Pombo

Abstract

Neurons and oligodendrocytes are terminally differentiated cells that perform highly specialized functions, which depend on cascades of gene activation and repression to retain homeostatic control over a lifespan. Gene expression is regulated by three-dimensional (3D) genome organisation, from local levels of chromatin compaction to the organisation of topological domains and chromosome compartments. Whereas our understanding of 3D genome architecture has vastly increased in the past decade, it remains difficult to study specialized cells in their native environment without disturbing their activity. To develop the application of Genome Architecture Mapping (GAM) in small numbers of specialized cells in complex tissues, we combined GAM with immunoselection. We applied immunoGAM to map the genome architecture of specific cell populations in the juvenile/adult mouse brain: dopaminergic neurons (DNs) from the midbrain, pyramidal glutamatergic neurons (PGNs) from the hippocampus, and oligodendrocyte lineage cells (OLGs) from the cortex. We integrate 3D genome organisation with single-cell transcriptomics data, and find specific chromatin structures that relate with cell-type specific patterns of gene expression. We discover abundan...Continue Reading

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Mentioned in this Paper

Endomembrane System
Patterns
Cellular Process
COPA
Transport Vesicles
Complex (molecular entity)
Trafficking
Intraflagellar Transport
Nuclear Pore Complex Proteins
Vesicle

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