Title: Cigarette smoke component acrolein modulates chromatin assembly by inhibiting histone acetylation.
Authors: Chen, Danqi; Fang, Lei; Li, Hongjie; Tang, Moon-shong; Jin, Chunyuan
Published In J Biol Chem, (2013 Jul 26)
Abstract: Chromatin structure and gene expression are both regulated by nucleosome assembly. How environmental factors influence histone nuclear import and the nucleosome assembly pathway, leading to changes in chromatin organization and transcription, remains unknown. Acrolein (Acr) is an α,β-unsaturated aldehyde, which is abundant in the environment, especially in cigarette smoke. It has recently been implicated as a potential major carcinogen of smoking-related lung cancer. Here we show that Acr forms adducts with histone proteins in vitro and in vivo and preferentially reacts with free histones rather than with nucleosomal histones. Cellular fractionation analyses reveal that Acr exposure specifically inhibits acetylations of N-terminal tails of cytosolic histones H3 and H4, modifications that are important for nuclear import and chromatin assembly. Notably, Acr exposure compromises the delivery of histone H3 into chromatin and increases chromatin accessibility. Moreover, changes in nucleosome occupancy at several genomic loci are correlated with transcriptional responses to Acr exposure. Our data provide new insights into mechanisms whereby environmental factors interact with the genome and influence genome function.
PubMed ID: 23770671
MeSH Terms: Acetylation/drug effects; Acetyltransferases/genetics; Acrolein/chemistry; Acrolein/metabolism*; Acrolein/pharmacology; Animals; Blotting, Western; Cell Line; Cell Line, Tumor; Chromatin Assembly and Disassembly/drug effects; Chromatin Assembly and Disassembly/genetics; Chromatin Assembly and Disassembly/physiology*; Cytosol/drug effects; Cytosol/metabolism; Early Growth Response Protein 2/genetics; Gene Expression/drug effects; Histones/chemistry; Histones/genetics; Histones/metabolism*; Humans; Inhibitor of Apoptosis Proteins/genetics; Intracellular Signaling Peptides and Proteins; Nucleosomes/drug effects; Nucleosomes/genetics; Nucleosomes/metabolism; Protein Binding; Proteins/genetics; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Smoke*; Tobacco/chemistry*; Xenopus; Xenopus Proteins/chemistry; Xenopus Proteins/genetics; Xenopus Proteins/metabolism