Homocitrullination is a novel histone H1 epigenetic mark dependent on aryl hydrocarbon receptor recruitment of carbamoyl phosphate synthase

Aditya D. Joshi, Mehnaz G. Mustafa, Cheryl F. Lichti, Cornelis Elferink

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27767-27778
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number46
DOIs
StatePublished - Nov 13 2015

Fingerprint

Carbamyl Phosphate
Aryl Hydrocarbon Receptors
Xenobiotics
Epigenomics
Histones
Response Elements
Chemical activation
Chromatin
Genes
Proteins
DNA
Post Translational Protein Processing
Nuclear Proteins
Gene expression
Transcriptional Activation
Lysine
Toxicity
Transcription Factors
Genome
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Homocitrullination is a novel histone H1 epigenetic mark dependent on aryl hydrocarbon receptor recruitment of carbamoyl phosphate synthase. / Joshi, Aditya D.; Mustafa, Mehnaz G.; Lichti, Cheryl F.; Elferink, Cornelis.

In: Journal of Biological Chemistry, Vol. 290, No. 46, 13.11.2015, p. 27767-27778.

Research output: Contribution to journalArticle

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