Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration Article Swipe
Natalie A. David
,
Robin D. Lee
,
Rebecca S. LaRue
,
Sookyong Joo
,
Michael A. Farrar
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.27.559810
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.27.559810
T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single-cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1 f/f x Ncor2 f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for the combined action of NCOR1 and NCOR2 over the course of thymocyte development.
Related Topics
Concepts
Corepressor
Biology
Nuclear receptor co-repressor 1
Nuclear receptor
Transcription factor
Cell biology
Chromatin remodeling
Chromatin
Histone
Thymocyte
Psychological repression
Downregulation and upregulation
Genetics
Gene
T cell
Gene expression
Immune system
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.09.27.559810
- https://www.biorxiv.org/content/biorxiv/early/2023/09/29/2023.09.27.559810.full.pdf
- OA Status
- green
- References
- 101
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4387159480
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4387159480Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.09.27.559810Digital Object Identifier
- Title
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Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigrationWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-09-29Full publication date if available
- Authors
-
Natalie A. David, Robin D. Lee, Rebecca S. LaRue, Sookyong Joo, Michael A. FarrarList of authors in order
- Landing page
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https://doi.org/10.1101/2023.09.27.559810Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/09/29/2023.09.27.559810.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/09/29/2023.09.27.559810.full.pdfDirect OA link when available
- Concepts
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Corepressor, Biology, Nuclear receptor co-repressor 1, Nuclear receptor, Transcription factor, Cell biology, Chromatin remodeling, Chromatin, Histone, Thymocyte, Psychological repression, Downregulation and upregulation, Genetics, Gene, T cell, Gene expression, Immune systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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101Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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