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

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

PROVIDER: PRJNA922863 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR23049226_1.fastq.gz	Fastqsanger.gz
	SRR23049226_2.fastq.gz	Fastqsanger.gz
	SRR23049227_1.fastq.gz	Fastqsanger.gz
	SRR23049227_2.fastq.gz	Fastqsanger.gz

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SATB2 organizes the 3D genome architecture of cognition in cortical neurons [Hi-C]

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SATB2 organizes the 3D genome architecture of cognition in cortical neurons [RNA-Seq]

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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.

2024-01-22 | GSE222609 | GEO

SATB2 organizes the 3D genome architecture of cognition in cortical neurons [CUT&RUN]

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2024-01-22 | GSE222607 | GEO

SATB2 organizes the 3D genome architecture of cognition in cortical neurons [Hi-C]

2024-01-22 | GSE222606 | GEO

SATB2 organizes the 3D genome architecture of cognition in cortical neurons [RNA-Seq]

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SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes

Project description:SATB2, encoding a nuclear chromosomal scaffolding protein, is a schizophrenia risk gene and genetically associated with human intelligence. How SATB2 affects cognition at molecular level is currently unknown. Our data suggest that interactions between SATB2 and the inner nuclear membrane protein LEMD2 orchestrate gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology. We show that LEMD2, a candidate component of the A-heterochromatin tether, binds to SATB2 and the two proteins exert overlapping cellular functions. SATB2 is essential for neuronal activity-triggered nuclear envelope plasticity, which requires LEMD2 as well as the ESCRT-III/VPS4 complex. LEMD2-depletion in cortical neurons, like SATB2 ablation, affects the expression of multiple neuronal activity-regulated genes. The gene-sets regulated by LEMD2 and SATB2 significantly overlap and the LEMD2 gene-set is enriched for SATB2-bound genes. In human genetic data, LEMD2-regulated genes are enriched for loss-of-function mutations reported in autism, intellectual disability and schizophrenia and are, like SATB2-regulated genes, associated with cognitive function.

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