FANS unfixed: isolation and proteomic analysis of mouse cell type-specific brain nuclei
Author(s)
Type
Journal Article
Abstract
Epigenetic-mediated gene regulation orchestrates brain cell-type gene expression programs, and epigenetic dysregulation is a major driver of aging and disease-associated changes. Proteins that mediate gene regulation are mostly localized to the nucleus; however, nuclear-localized proteins are often underrepresented in gene expression studies and have been understudied in the context of the brain. To address this challenge, we have optimized an approach for nuclei isolation that is compatible with proteomic analysis. This was coupled to a mass spectrometry protocol for detecting proteins in low-concentration samples. We have generated nuclear proteomes for neurons, microglia, and oligodendrocytes from the mouse brain cortex and identified cell-type nuclear proteins associated with chromatin structure and organization, chromatin modifiers such as transcription factors, and RNA-binding proteins, among others. Our nuclear proteomics platform paves the way for assessing brain cell type changes in the nuclear proteome across health and disease, such as neurodevelopmental, aging, neurodegenerative, and neuroinflammatory conditions. Data are available via ProteomeXchange with the identifier PXD053515.
Date Issued
2024-07-26
Date Acceptance
2024-07-12
Citation
Journal of Proteome Research, 2024, 23 (9), pp.3847-3857
ISSN
1535-3893
Publisher
American Chemical Society
Start Page
3847
End Page
3857
Journal / Book Title
Journal of Proteome Research
Volume
23
Issue
9
Copyright Statement
Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39056441
Subjects
ALZHEIMERS-DISEASE
Biochemical Research Methods
Biochemistry & Molecular Biology
cell-type-specific
epigenetics
EXPRESSION
FANS
GENE
HISTONE-DEACETYLASE-2
Life Sciences & Biomedicine
MECHANISMS
microglia
MICROGLIA
MUTATIONS
neurons
oligodendrocytes
proteomics
Science & Technology
SELECTION
S-NITROSYLATION
SPECTRUM
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-07-26