The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

Giulia Saredi; Francesco N. Carelli; Stéphane G. M. Rolland; Giulia Furlan; Sandra Piquet; Alex Appert; Luis Sanchez-Pulido; Jonathan L. Price; Pablo Alcon; Lisa Lampersberger; Anne-Cécile Déclais; Navin B. Ramakrishna; Rachel Toth; Thomas Macartney; Constance Alabert; Chris P. Ponting; Sophie E. Polo; Eric A. Miska; Anton Gartner; Julie Ahringer; John Rouse

doi:10.1038/s41594-023-01204-3

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

Giulia Saredi (Lead / Corresponding author), Francesco N. Carelli, Stéphane G. M. Rolland, Giulia Furlan, Sandra Piquet, Alex Appert, Luis Sanchez-Pulido, Jonathan L. Price, Pablo Alcon, Lisa Lampersberger, Anne-Cécile Déclais, Navin B. Ramakrishna, Rachel Toth, Thomas Macartney, Constance Alabert, Chris P. Ponting, Sophie E. Polo, Eric A. Miska, Anton Gartner, Julie AhringerJohn Rouse (Lead / Corresponding author)

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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 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.

Original language	English
Pages (from-to)	523-535
Number of pages	13
Journal	Nature Structural & Molecular Biology
Volume	31
Issue number	3
Early online date	18 Jan 2024
DOIs	https://doi.org/10.1038/s41594-023-01204-3
Publication status	Published - Mar 2024

Keywords

Chromatin
Epigenetics

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10.1038/s41594-023-01204-3Licence: CC BY

Final published versionFinal published version, 10.3 MBLicence: CC BY

DNA Interstrand Crosslink Repair and Chromatin Remodelling (ICL CHROM)
Rouse, J. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/02/20 → 26/04/22
Project: Research
Impact of DNA Replication on Epigenetics (IDRE)
Alabert, C. (Investigator) & Owen-Hughes, T. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/05/17 → 31/05/24
Project: Research

Cite this

Saredi, G., Carelli, F. N., Rolland, S. G. M., Furlan, G., Piquet, S., Appert, A., Sanchez-Pulido, L., Price, J. L., Alcon, P., Lampersberger, L., Déclais, A.-C., Ramakrishna, N. B., Toth, R., Macartney, T., Alabert, C., Ponting, C. P., Polo, S. E., Miska, E. A., Gartner, A., ... Rouse, J. (2024). The histone chaperone SPT2 regulates chromatin structure and function in Metazoa. Nature Structural & Molecular Biology, 31(3), 523-535. https://doi.org/10.1038/s41594-023-01204-3

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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 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.",

keywords = "Chromatin, Epigenetics",

author = "Giulia Saredi and Carelli, {Francesco N.} and Rolland, {St{\'e}phane G. M.} and Giulia Furlan and Sandra Piquet and Alex Appert and Luis Sanchez-Pulido and Price, {Jonathan L.} and Pablo Alcon and Lisa Lampersberger and Anne-C{\'e}cile D{\'e}clais and Ramakrishna, {Navin B.} and Rachel Toth and Thomas Macartney and Constance Alabert and Ponting, {Chris P.} and Polo, {Sophie E.} and Miska, {Eric A.} and Anton Gartner and Julie Ahringer and John Rouse",

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year = "2024",

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doi = "10.1038/s41594-023-01204-3",

language = "English",

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Saredi, G, Carelli, FN, Rolland, SGM, Furlan, G, Piquet, S, Appert, A, Sanchez-Pulido, L, Price, JL, Alcon, P, Lampersberger, L, Déclais, A-C, Ramakrishna, NB, Toth, R, Macartney, T, Alabert, C, Ponting, CP, Polo, SE, Miska, EA, Gartner, A, Ahringer, J & Rouse, J 2024, 'The histone chaperone SPT2 regulates chromatin structure and function in Metazoa', Nature Structural & Molecular Biology, vol. 31, no. 3, pp. 523-535. https://doi.org/10.1038/s41594-023-01204-3

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T1 - The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

AU - Saredi, Giulia

AU - Carelli, Francesco N.

AU - Rolland, Stéphane G. M.

AU - Furlan, Giulia

AU - Piquet, Sandra

AU - Appert, Alex

AU - Sanchez-Pulido, Luis

AU - Price, Jonathan L.

AU - Alcon, Pablo

AU - Lampersberger, Lisa

AU - Déclais, Anne-Cécile

AU - Ramakrishna, Navin B.

AU - Toth, Rachel

AU - Macartney, Thomas

AU - Alabert, Constance

AU - Ponting, Chris P.

AU - Polo, Sophie E.

AU - Miska, Eric A.

AU - Gartner, Anton

AU - Ahringer, Julie

AU - Rouse, John

PY - 2024/3

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N2 - 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.

AB - 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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KW - Epigenetics

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DO - 10.1038/s41594-023-01204-3

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C2 - 38238586

SN - 1545-9993

VL - 31

SP - 523

EP - 535

JO - Nature Structural & Molecular Biology

JF - Nature Structural & Molecular Biology

IS - 3

ER -

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

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Keywords

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Projects

DNA Interstrand Crosslink Repair and Chromatin Remodelling (ICL CHROM)

Impact of DNA Replication on Epigenetics (IDRE)

Cite this