title: A novel role for protein arginine deiminase 4 in pluripotency: the emerging role of citrullinated histone H1 in cellular programming.
abstract: Histone post-translational modifications (PTMs) alter the chromatin architecture, generating "open" and "closed" states, and these structural changes can modulate gene expression under specific cellular conditions. While methylation and acetylation are the best-characterized histone PTMs, citrullination by the protein arginine deiminases (PADs) represents another important player in this process. In addition to "fine tuning" chromatin structure at specific loci, histone citrullination can also promote rapid global chromatin decondensation during the formation of extracellular traps (ETs) in immune cells. Recent studies now show that PAD4-mediated citrullination of histone H1 at promoter elements can also promote localized chromatin decondensation in stem cells, thus regulating the pluripotent state. These observations suggest that PAD-mediated histone deimination profoundly affects chromatin structure, possibly above and beyond that of other PTMs. Additionally, these recent findings further enhance our understanding of PAD biology and the important contributions that these enzymes play in development, health, and disease.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Slade
authors.forename: Sachi
authors.initials: S
authors.lastname: Horibata
authors.forename: Scott A
authors.initials: SA
authors.lastname: Coonrod
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D065150:Cellular Reprogramming; D042002:Chromatin Assembly and Disassembly; D002956:Citrulline / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000502:physiology*; D057026:Induced Pluripotent Stem Cells / Q000201:enzymology*; D011499:Protein Processing, Post-Translational; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D014157:Transcription Factors; D002956:Citrulline; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: cancer; chromatin; deiminase; gene regulation; histone; pluripotency; rheumatoid arthritis; stem cells