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SATB2 organizes the 3D genome architecture of cognition in cortical neurons [ATAC-seq]

ABSTRACT: The DNA-binding protein SATB2 is genetically linked to human intelligence. We studied its influence on 3D epigenome by mapping chromatin interactions and accessibility in control versus SATB2-deficient cortical neurons. We find that SATB2 affects the chromatin looping between enhancers and promoters of neuronal activity-regulated genes, thus influencing their expression. It also alters A/B compartments, Topologically Associating Domains and Frequently Interacting Regions. Genes linked to SATB2-dependent 3D genome changes are implicated in highly specialized neuronal functions and contribute to cognitive ability and risk for neuropsychiatric and neurodevelopmental disorders. Non-coding DNA regions with SATB2-dependent structure are enriched for common variants associated with educational attainment, intelligence and schizophrenia. Our data establish SATB2 as a cell-type specific 3D genome modulator, which operates both independently and in cooperation with CTCF to set up the chromatin landscape of pyramidal neurons for cognitive processes.

ORGANISM(S): Mus musculus

PROVIDER: GSE222607 | GEO | 2024/01/22

REPOSITORIES: GEO

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SATB2 organizes the 3D genome architecture of cognition in cortical neurons

Project description:The DNA-binding protein SATB2 is genetically linked to human intelligence. We studied its influence on 3D epigenome by mapping chromatin interactions and accessibility in control versus SATB2-deficient cortical neurons. We find that SATB2 affects the chromatin looping between enhancers and promoters of neuronal activity-regulated genes, thus influencing their expression. It also alters A/B compartments, Topologically Associating Domains and Frequently Interacting Regions. Genes linked to SATB2-dependent 3D genome changes are implicated in highly specialized neuronal functions and contribute to cognitive ability and risk for neuropsychiatric and neurodevelopmental disorders. Non-coding DNA regions with SATB2-dependent structure are enriched for common variants associated with educational attainment, intelligence and schizophrenia. Our data establish SATB2 as a cell-type specific 3D genome modulator, which operates both independently and in cooperation with CTCF to set up the chromatin landscape of pyramidal neurons for cognitive processes.

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