Genes encoding SATB2-interacting proteins in adult cerebral cortex contribute to human cognitive ability.
Adult
Animals
Cognition
/ physiology
Humans
Matrix Attachment Region Binding Proteins
/ genetics
Memory, Long-Term
/ physiology
Mice
Mice, Inbred C57BL
Neocortex
/ physiology
Neurons
/ physiology
Polymorphism, Single Nucleotide
/ genetics
Transcription Factors
/ genetics
Transcription, Genetic
/ genetics
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
11
07
2018
accepted:
12
12
2018
entrez:
7
2
2019
pubmed:
7
2
2019
medline:
12
3
2019
Statut:
epublish
Résumé
During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In the adult CNS, SATB2 is expressed in pyramidal neurons of all cortical layers and is a regulator of synaptic plasticity and long-term memory. Common variation in SATB2 locus confers risk of schizophrenia, whereas rare, de novo structural and single nucleotide variants cause severe intellectual disability and absent or limited speech. To characterize differences in SATB2 molecular function in developing vs adult neocortex, we isolated SATB2 protein interactomes at the two ontogenetic stages and identified multiple novel SATB2 interactors. SATB2 interactomes are highly enriched for proteins that stabilize de novo chromatin loops. The comparison between the neonatal and adult SATB2 protein complexes indicates a developmental shift in SATB2 molecular function, from transcriptional repression towards organization of chromosomal superstructure. Accordingly, gene sets regulated by SATB2 in the neocortex of neonatal and adult mice show limited overlap. Genes encoding SATB2 protein interactors were grouped for gene set analysis of human GWAS data. Common variants associated with human cognitive ability are enriched within the genes encoding adult but not neonatal SATB2 interactors. Our data support a shift in the function of SATB2 in cortex over lifetime and indicate that regulation of spatial chromatin architecture by the SATB2 interactome contributes to cognitive function in the general population.
Identifiants
pubmed: 30726206
doi: 10.1371/journal.pgen.1007890
pii: PGENETICS-D-18-01411
pmc: PMC6364870
doi:
Substances chimiques
Matrix Attachment Region Binding Proteins
0
SATB2 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007890Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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