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Ybx1 fine-tunes PRC2 activities to control embryonic brain development
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Chromatin modifiers affect spatiotemporal gene expression programs that underlie organismal development. The Polycomb repressive complex 2 (PRC2) is a crucial chromatin modifier in executing neurodevelopmental programs. Here, we find that PRC2 interacts with the nucleic acid–binding protein Ybx1. In the mouse embryo in vivo, Ybx1 is required for forebrain specification and restricting mid-hindbrain growth. In neural progenitor cells (NPCs), Ybx1 controls self-renewal and neuronal differentiation. Mechanistically, Ybx1 highly overlaps PRC2 binding genome-wide, controls PRC2 distribution, and inhibits H3K27me3 levels. These functions are consistent with Ybx1-mediated promotion of genes involved in forebrain specification, cell proliferation, or neuronal differentiation. In Ybx1-knockout NPCs, H3K27me3 reduction by PRC2 enzymatic inhibitor or genetic depletion partially rescues gene expression and NPC functions. Our findings suggest that Ybx1 fine-tunes PRC2 activities to regulate spatiotemporal gene expression in embryonic neural development and uncover a crucial epigenetic mechanism balancing forebrain–hindbrain lineages and self-renewal–differentiation choices in NPCs.<br />Polycomb repressive complex 2 (PRC2) methylates H3K27 and suppresses RNA polymerase II transcription by promoting a closed chromatin. Here the authors identify the transcription factor Ybx1 as an interactor that regulates the binding of PRC2 to chromatin and H3K27 methylation to promote the genetic programs underlying neural lineages and neural progenitor self-renewal–differentiation choices.
- Subjects :
- 0301 basic medicine
Fluorescent Antibody Technique
General Physics and Astronomy
RNA polymerase II
02 engineering and technology
Epigenesis, Genetic
Mice
Transcription (biology)
Histone post-translational modifications
Gene expression
Epigenetics in the nervous system
lcsh:Science
Cells, Cultured
Mice, Knockout
Multidisciplinary
biology
Reverse Transcriptase Polymerase Chain Reaction
Brain
Cell Differentiation
Flow Cytometry
021001 nanoscience & nanotechnology
Chromatin
Cell biology
Spatiotemporal gene expression
Embryogenesis
Drosophila
0210 nano-technology
PRC2
Neural development
Chromatin Immunoprecipitation
Science
Blotting, Western
Developmental neurogenesis
macromolecular substances
Methylation
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Animals
Immunoprecipitation
Transcription factor
Cell Proliferation
fungi
Histone-Lysine N-Methyltransferase
General Chemistry
030104 developmental biology
biology.protein
lcsh:Q
Protein Processing, Post-Translational
Transcription Factors
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....34c510ff47b6814e215607dec48fa6d1