A novel role for protein arginine deiminase 4 in pluripotency: the emerging role of citrullinated histone H1 in cellular programming.

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Animals; Arthritis, Rheumatoid; Cellular Reprogramming; Chromatin Assembly and Disassembly; Citrulline; Histones; Humans; Hydrolases; Induced Pluripotent Stem Cells; Protein Processing, Post-Translational; Transcription Factors; Transcription, Genetic


Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


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.

DOI of Published Version



Bioessays. 2014 Aug;36(8):736-40. doi: 10.1002/bies.201400057. Epub 2014 May 30. Link to article on publisher's site

Journal/Book/Conference Title

BioEssays : news and reviews in molecular, cellular and developmental biology


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed