The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

作者：Giulia Saredi, Francesco N. Carelli, S. Rolland, Giulia Furlan, Sandra Piquet, Alex Appert, Luis Sánchez‐Pulido, Jonathan Price, Pablo Alcón, 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 · 发表于：Nature Structural & Molecular Biology · 年份：2024 · DOI：10.1038/s41594-023-01204-3 · 被引用次数：4 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、Epigenetics and DNA Methylation

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.