PXD032742 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Developmental disruption to the cortical transcriptome and synaptosome in a model of SETD1A loss-of-function |
Description | Large-scale genomic studies of schizophrenia implicate genes involved in the epigenetic regulation of transcription by histone methylation and genes encoding components of the synapse. However, the interactions between these pathways in conferring risk to psychiatric illness are unknown. Loss-of-function (LoF) mutations in the gene encoding histone methyltransferase, SETD1A, confer substantial risk to schizophrenia. Among several roles, SETD1A is thought to be involved in the development and function of neuronal circuits. Here, we employed a multi-omics approach to study the effects of heterozygous Setd1a LoF on gene expression and synaptic composition in mouse cortex across five developmental timepoints from embryonic day 14 to postnatal day 70. Using RNA sequencing, we observed that Setd1a LoF resulted in the consistent downregulation of genes enriched for mitochondrial pathways. This effect extended to the synaptosome, in which we found age-specific disruption to both mitochondrial and synaptic proteins. Using large-scale patient genomics data, we observed no enrichment for genetic association with schizophrenia within differentially expressed transcripts or proteins, suggesting they derive from a distinct mechanism of risk from that implicated by genomic studies. This study highlights biological pathways through which SETD1A loss-of-function may confer risk to schizophrenia. Further work is required to determine whether the effects observed in this model reflect human pathology. |
HostingRepository | PRIDE |
AnnounceDate | 2022-05-26 |
AnnouncementXML | Submission_2022-05-26_05:35:18.843.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mark Collins |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-23 07:30:30 | ID requested | |
⏵ 1 | 2022-05-26 05:35:19 | announced | |
Publication List
Clifton NE, Bosworth ML, Haan N, Rees E, Holmans PA, Wilkinson LS, Isles AR, Collins MO, Hall J, Developmental disruption to the cortical transcriptome and synaptosome in a model of SETD1A loss-of-function. Hum Mol Genet, 31(18):3095-3106(2022) [pubmed] |
Keyword List
submitter keyword: SETD1A, Schizophrenia, Development, Neuronal, Synaptosome |
Contact List
Mark Collins |
contact affiliation | School of Biosciences University of Sheffield Sheffield, S10 2TN United Kingdom |
contact email | mark.collins@sheffield.ac.uk |
lab head | |
Mark Collins |
contact affiliation | University of Sheffield |
contact email | mark.collins@sheffield.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032742
- Label: PRIDE project
- Name: Developmental disruption to the cortical transcriptome and synaptosome in a model of SETD1A loss-of-function