Title: Homocitrullination Is a Novel Histone H1 Epigenetic Mark Dependent on Aryl Hydrocarbon Receptor Recruitment of Carbamoyl Phosphate Synthase 1.
Authors: Joshi, Aditya D; Mustafa, Mehnaz G; Lichti, Cheryl F; Elferink, Cornelis J
Published In J Biol Chem, (2015 Nov 13)
Abstract: The aryl hydrocarbon receptor (AhR), a regulator of xenobiotic toxicity, is a member of the eukaryotic Per-Arnt-Sim domain protein family of transcription factors. Recent evidence identified a novel AhR DNA recognition sequence called the nonconsensus xenobiotic response element (NC-XRE). AhR binding to the NC-XRE in response to activation by the canonical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in concomitant recruitment of carbamoyl phosphate synthase 1 (CPS1) to the NC-XRE. Studies presented here demonstrate that CPS1 is a bona fide nuclear protein involved in homocitrullination (hcit), including a key lysine residue on histone H1 (H1K34hcit). H1K34hcit represents a hitherto unknown epigenetic mark implicated in enhanced gene expression of the peptidylarginine deiminase 2 gene, itself a chromatin-modifying protein. Collectively, our data suggest that AhR activation promotes CPS1 recruitment to DNA enhancer sites in the genome, resulting in a specific enzyme-independent post-translational modification of the linker histone H1 protein (H1K34hcit), pivotal in altering local chromatin structure and transcriptional activation.
PubMed ID: 26424795
MeSH Terms: Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors/metabolism*; Carbamoyl-Phosphate Synthase (Ammonia)/metabolism*; Cells, Cultured; Chromatin/metabolism; Chromatin/ultrastructure; Citrulline/analogs & derivatives*; Citrulline/metabolism; Epigenesis, Genetic*; Female; Histones/metabolism*; Hydrolases/genetics; Lysine/metabolism; Mice; Mice, Inbred C57BL; Nuclear Proteins/metabolism*; Polychlorinated Dibenzodioxins/metabolism; Protein Binding; Protein Processing, Post-Translational; Protein Structure, Tertiary; Protein-Arginine Deiminases; Receptors, Aryl Hydrocarbon/metabolism*; Response Elements; Transcriptional Activation