Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk.
Science
; 362(6420)2018 12 14.
Article
em En
| MEDLINE
| ID: mdl-30545851
ABSTRACT
To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type-specific disease risk vulnerabilities in spatial genome organization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Cromossomos Humanos
/
Regulação da Expressão Gênica no Desenvolvimento
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Predisposição Genética para Doença
/
Epigênese Genética
/
Neurogênese
/
Células-Tronco Neurais
/
Conectoma
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Science
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos