Binding to nucleosome poises human SIRT6 for histone H3 deacetylation.

ABSTRACT: Sirtuin 6 (SIRT6) is an NAD⁺-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here, we present the structure of human SIRT6 bound to a nucleosome determined by cryogenic electron microscopy. The zinc finger domain of SIRT6 associates tightly with the acidic patch of the nucleosome through multiple arginine anchors. The Rossmann fold domain binds to the terminus of the looser DNA half of the nucleosome, detaching two turns o

SUBMITTER: Smirnova E 

PROVIDER: S-EPMC10942634 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature