Ectopic histone clipping in the mouse model of progressive myoclonus epilepsy Article Swipe
Eduard Daura
,
Saara Tegelberg
,
Masahito Yoshihara
,
Christopher B. Jackson
,
Francesca Simonetti
,
Katri Aksentjeff
,
Sini Ezer
,
Paula Hakala
,
Shintaro Katayama
,
Juha Kere
,
Anna‐Elina Lehesjoki
,
Tarja Joensuu
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.08.21.261180
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.08.21.261180
We establish cystatin B (CSTB) as a regulator of histone H3 tail clipping in murine neural progenitor cells (NPCs) and provide evidence suggesting that epigenetic dysregulation contributes to the early pathogenesis in brain disorders associated with deficient CSTB function. We show that NPCs undergo regulated cleavage of the N-terminal tail of histone H3 at threonine 22 (H3T22) transiently upon induction of differentiation. CSTB-deficient NPCs present premature activation of H3T22 clipping during self-renewal mediated by increased activity of cathepsins L and B. During differentiation, the proportion of immature committed neurons undergoing H3T22 clipping is significantly higher in CSTB-deficient than in wild-type NPCs, with no observable decline within 12 days post-differentiation. CSTB-deficient NPCs exhibit significant transcriptional changes highlighting altered expression of nuclear-encoded mitochondrial genes. These changes are associated with significantly impaired respiratory capacity of differentiating NPCs devoid of CSTB. Our data expand the mechanistic understanding of diseases associated with CSTB deficiency.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2020.08.21.261180
- https://www.biorxiv.org/content/biorxiv/early/2020/08/22/2020.08.21.261180.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 78
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3081152108
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Raw OpenAlex JSON
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https://openalex.org/W3081152108Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2020.08.21.261180Digital Object Identifier
- Title
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Ectopic histone clipping in the mouse model of progressive myoclonus epilepsyWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
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2020-08-22Full publication date if available
- Authors
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Eduard Daura, Saara Tegelberg, Masahito Yoshihara, Christopher B. Jackson, Francesca Simonetti, Katri Aksentjeff, Sini Ezer, Paula Hakala, Shintaro Katayama, Juha Kere, Anna‐Elina Lehesjoki, Tarja JoensuuList of authors in order
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https://doi.org/10.1101/2020.08.21.261180Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2020/08/22/2020.08.21.261180.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/2020/08/22/2020.08.21.261180.full.pdfDirect OA link when available
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Biology, Histone, Cell biology, Ectopic expression, Epigenetics, Histone H3, Neuroscience, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2021: 1Per-year citation counts (last 5 years)
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78Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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