H3 citrullination cross-talk within the histone code

As an understudied protein post translational modification (PTM), positively charged arginine is converted to neutral citrulline (Rcit) by peptidylarginine deiminase (PAD) enzymes, with no known means of reversal. The PTM is particularly extensive in NETosis, a form of neutrophil programmed cell death with an extensive citrullinome characterized by Neutrophil Extracellular Traps (NETs).

Here the Citrullinome is extensive and includes the citrullination of histone tails neutralizes arginine charge and is linked to chromatin de-condensation during extracellular release. Given its assumed irreversibility, any role for histone citrullination outside of terminal NETosis is controversial. However, any investigation of site-specific histone Rcit(s) in combinatorial chromatin regulation is severely hindered by the lack of reliable detection reagents.