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J Biol Chem. 2015 Nov 13;290(46):27767-78. doi: 10.1074/jbc.M115.678144. Epub 2015 Sep 30.

Homocitrullination Is a Novel Histone H1 Epigenetic Mark Dependent on Aryl Hydrocarbon Receptor Recruitment of Carbamoyl Phosphate Synthase 1.

Author information

1
From the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 and.
2
Protea, Morgantown, West Virginia 26505.
3
From the Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 and coelferi@utmb.edu.

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.

KEYWORDS:

aryl hydrocarbon receptor (AhR) (AHR); chromatin modification; dioxin; gene regulation; hepatocyte

PMID:
26424795
PMCID:
PMC4646023
DOI:
10.1074/jbc.M115.678144
[Indexed for MEDLINE]
Free PMC Article

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