The histone chaperone activity of SPT2 controls chromatin structure and function in Metazoa

Saredi, G.; Carelli, F. N.; Furlan, G.; Rolland, S.; Piquet, S.; Appert, A.; Sanchez-Pulido, L.; Price, J. L.; Alcon, P.; Lampersberger, L.; Declais, A.-C.; Ramakrishna, N. B.; Toth, R.; Ponting, C. P.; Polo, S. E.; Miska, E. A.; Ahringer, J.; Gartner, A.; Rouse, J.

doi:10.1101/2023.02.16.528451

bioRxiv · 10.1101/2023.02.16.528451

The histone chaperone activity of SPT2 controls chromatin structure and function in Metazoa

Saredi, G.·Carelli, F. N.·Furlan, G.·Rolland, S.·Piquet, S.·Appert, A.·Sanchez-Pulido, L.·Price, J. L.·Alcon, P.·Lampersberger, L.·Declais, A.-C.·Ramakrishna, N. B.·Toth, R.·Ponting, C. P.·Polo, S. E.·Miska, E. A.·Ahringer, J.·Gartner, A.·Rouse, J.

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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 orthologue 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 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 these loci. We also show that human SPT2 controls the incorporation of new H3.3 into chromatin. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.

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Saredi, G., Carelli, F. N., Furlan, G., Rolland, S., Piquet, S., Appert, A., Sanchez-Pulido, L., Price, J. L., Alcon, P., Lampersberger, L., Declais, A.-C., Ramakrishna, N. B., Toth, R., Ponting, C. P., Polo, S. E., Miska, E. A., Ahringer, J., Gartner, A., Rouse, J.. 2023-02-16. The histone chaperone activity of SPT2 controls chromatin structure and function in Metazoa. https://doi.org/10.1101/2023.02.16.528451

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