The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

Author:

Saredi GiuliaORCID,Carelli Francesco N.,Rolland Stéphane G. M.,Furlan Giulia,Piquet Sandra,Appert Alex,Sanchez-Pulido Luis,Price Jonathan L.,Alcon PabloORCID,Lampersberger Lisa,Déclais Anne-CécileORCID,Ramakrishna Navin B.ORCID,Toth RachelORCID,Macartney ThomasORCID,Alabert Constance,Ponting Chris P.,Polo Sophie E.ORCID,Miska Eric A.ORCID,Gartner Anton,Ahringer Julie,Rouse JohnORCID

Abstract

AbstractHistone 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.

Publisher

Springer Science and Business Media LLC

Subject

Molecular Biology,Structural Biology

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