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The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

Saredi, Giulia LU ; Carelli, Francesco N ; Rolland, Stéphane G M ; Furlan, Giulia ; Piquet, Sandra ; Appert, Alex ; Sanchez-Pulido, Luis ; Price, Jonathan L ; Alcon, Pablo and Lampersberger, Lisa , et al. (2024) In Nature Structural & Molecular Biology 31(3). p.523-535
Abstract

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin... (More)

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.

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publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Humans, Histone Chaperones/genetics, DNA-Binding Proteins/metabolism, Histones/metabolism, Chromatin/metabolism, Nucleosomes/metabolism, Saccharomyces cerevisiae/metabolism
in
Nature Structural & Molecular Biology
volume
31
issue
3
pages
523 - 535
publisher
Nature Publishing Group
external identifiers
  • pmid:38238586
  • scopus:85182639268
ISSN
1545-9985
DOI
10.1038/s41594-023-01204-3
language
English
LU publication?
no
additional info
© 2024. The Author(s).
id
ce135439-d293-4220-a162-bca94d1ef540
date added to LUP
2025-11-03 11:00:07
date last changed
2025-12-16 07:53:22
@article{ce135439-d293-4220-a162-bca94d1ef540,
  abstract     = {{<p>Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.</p>}},
  author       = {{Saredi, Giulia and Carelli, Francesco N and Rolland, Stéphane G M and Furlan, Giulia and Piquet, Sandra and Appert, Alex and Sanchez-Pulido, Luis and Price, Jonathan L and Alcon, Pablo and Lampersberger, Lisa and Déclais, Anne-Cécile and Ramakrishna, Navin B and Toth, Rachel and Macartney, Thomas and Alabert, Constance and Ponting, Chris P and Polo, Sophie E and Miska, Eric A and Gartner, Anton and Ahringer, Julie and Rouse, John}},
  issn         = {{1545-9985}},
  keywords     = {{Animals; Humans; Histone Chaperones/genetics; DNA-Binding Proteins/metabolism; Histones/metabolism; Chromatin/metabolism; Nucleosomes/metabolism; Saccharomyces cerevisiae/metabolism}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{523--535}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Structural & Molecular Biology}},
  title        = {{The histone chaperone SPT2 regulates chromatin structure and function in Metazoa}},
  url          = {{http://dx.doi.org/10.1038/s41594-023-01204-3}},
  doi          = {{10.1038/s41594-023-01204-3}},
  volume       = {{31}},
  year         = {{2024}},
}