Homocitrullination is a Novel Histone H1 Epigenetic Mark Dependent on Aryl Hydrocarbon Receptor Recruitment of Carbamoyl Phosphate Synthase 1 [Gene Regulation]

September 30th, 2015 by Joshi, A. D., Mustafa, M. G., Lichti, C. F., Elferink, C. J.

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 non-consensus 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 (PTM) of the linker histone H1 protein (H1K34hcit), pivotal in altering local chromatin structure and transcriptional activation.
  • Posted in Journal of Biological Chemistry, Publications
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