Histone Arg modifications in transcription

Recent work by us and others has found that (1) promoter specific conversion of methyl-Arg to citrulline catalyzed by peptidylarginine deiminase 4 (PAD4/PADI4) regulates the expression of specific genes, such as p53 and estrogen receptor target genes; (2) albeit histone Arg demethylase remains elusive, it is formally possible that reversible Arg methylation and demethylation occurs during gene regulation. (Figure 2)

Figure 2. Many possible enzymatic mechanisms underlying histone/protein Arg modifications, including methylation by protein Arg methyltransferases (PRMTs); deimination and demethylimination catalyzed by peptidylarginine deiminase 4 (PAD4) to produce citrulline; however, whether JMJD6 plays a role as Arg demethylase needs to be resolved.
 

Citrullination in higher order chromatin structure

Multiple histone residues (e.g., histone H3 N-terminal tails) are modified by acetylation, citrullination, methylation, and phosphorylation, collectively referred as a "histone code" (Figure 3). Chromatin condensation/decondensation is regulated at multiple levels inside cell neucleus, including (1) organization of DNA with histones to form the nucleosome polymers; (2) compaction of nucleosomes by linker DNA and histone H1 to form 30 nm chromatin fibers; (3) organization of chromatin fibers by nuclear envelope and nucleolus. We currently investigate how citrullination regulates high order chromatin structure in neutrophils after bacterial infection.