The Schizophrenia Risk Gene Product Satb2 Regulates miRNAs Expression and Long-Term Memory in Adult CNS
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77005 | GEO | 2016/12/12
SECONDARY ACCESSION(S): PRJNA309578
REPOSITORIES: GEO
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Project description: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 which extent symptoms in SATB2-related human pathologies depend on developmental or adult functions of the protein remains to be established. To characterize differences in SATB2 molecular function in developing vs adult neocortex, we compared SATB2 protein interactomes and SATB2-driven gene expression programs at the two ontogenetic stages by co-IP mass spectrometry and RNAseq analyses, respectively. Our results demonstrated that 1) SATB2 interacts with different protein networks at the two ontogenetic stages, with a switch from transcriptional repression towards organization of chromatin structure and 2) SATB2 determines differential transcriptional programs in neonatal vs adult cortex.
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Project description:The goal of the study was to identify the binding site of SATB2 in wild-ype cortex by performing ChIP-seq using SATB2 antibody. E15 cortical tissues were dissected, lysed and fixed. Chromatin was prepared by sonication. Sequences bound by SATB2 protein was precipitated using a SATB2 antibody. Sequencing was performed on Illumina Genome Analyzer II. SATB2 binding peaks were called using MACS. ChIP for Satb2, followed by sequencing on Illumina Genome Analyzer II platform
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Project description:We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets.
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Project description:Satb1 and Satb2 are regulators of higher order chromatin in T cells and osteoblasts repectively. We were interested if Satb1 and Satb2 play a role in the regulation of gene expression in ES cells. This SuperSeries is composed of the following subset Series: GSE17487: Expression data in WT and Satb1-/- ES cells GSE17488: Expression data in WT and ES cells overexpressing Satb1 GSE17489: Expression data in WT and ES cells overexpressing Satb2 Refer to individual Series
2009-09-01 | E-GEOD-17490 | biostudies-arrayexpress
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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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 | GSE222608 | GEO
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 | GSE222607 | GEO
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 | GSE244285 | GEO
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 | GSE222606 | GEO
Project description:The goal of the study was to identify the binding site of SATB2 in wild-ype cortex by performing ChIP-seq using SATB2 antibody. E15 cortical tissues were dissected, lysed and fixed. Chromatin was prepared by sonication. Sequences bound by SATB2 protein was precipitated using a SATB2 antibody. Sequencing was performed on Illumina Genome Analyzer II. SATB2 binding peaks were called using MACS.
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