Isonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug isoniazid.

ABSTRACT: Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (K_inic), also called 4-picolinylation, in cells and mice. INH promotes the biosynthesis of isonicotinyl-CoA (Inic-CoA), a co-factor of intracellular isonicotinylation. Mass spectrometry reveals 26 K_inic sites in histones in HepG2 cells. Acetyltransferases CREB-binding protein (CBP) and P300 catalyse histone K_inic, while histone deacetylase HDAC3 functions as a deisonicotinylase. Notably, MNase sensitivity assay and RNA-seq analysis show that histone K_inic relax

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC8452692 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature