Arginine deiminases catalyse the conversion of arginine into citrulline by removing an amino group from the arginine molecule. Whilst arginine deiminases are primarily known for their roles in metabolism, immune evasion, and post-translational modifications, such as citrullination, their involvement in chromatin regulation is an emerging area of research. Protein-Arginine Deiminase Type-6 (PADT6) for example is predominantly expressed in the testes and is involved in spermatogenesis. It citrullinates specific proteins, including histones, in developing sperm cells in a process that may be essential for proper chromatin remodelling during sperm maturation. Arginine deiminases can influence chromatin structure and gene expression indirectly through the process of citrullination. In this context, citrullination refers to the post-translational modification of histone proteins, particularly histone H3, where arginine residues are converted into citrulline. This conversion leads to changes in histone charge and chromatin structure, which can have downstream effects on gene expression. An example of arginine deiminase involvement in chromatin regulation is the role of Peptidylarginine Deiminase 4 (PAD4) a calcium-dependent enzyme that citrullinates histones, in neutrophil extracellular trap (NET) formation. Neutrophils are activated in response to infection or inflammation, with PAD4 activated by calcium influx. PAD4 translocates to the nucleus and catalyses the conversion of arginine residues in histone H3 to citrulline, leading to the de-condensation of chromatin and the relaxation of DNA. As the chromatin decondenses, it mixes with cytoplasmic granules containing antimicrobial proteins and proteases, including myeloperoxidase (MPO), neutrophil elastase, and cathepsin G. The relaxed chromatin, now decorated with citrullinated histones, is expelled from the neutrophil in the form of NETs in a process known as NETosis. This release can occur in different ways: 1) Suicidal NETosis. This is the classical form of NETosis, where the cell undergoes programmed cell death. The cell membrane ruptures, releasing the NETs along with other cellular contents; 2) Vital NETosis. In this process, the cell remains viable and can continue to function. The NETs are released without cell lysis through a process involving vesicles called cytoplasts. The primary function of NETs is to capture and immobilize pathogens. The DNA fibres in NETs create a barrier that traps bacteria, fungi, and other microbes, preventing them from spreading. NETs can modulate the immune response by activating other immune cells and releasing cytokines, thereby helping to coordinate the immune response to eliminate the infection. In some cases, NETs may not be efficiently cleared, leading to tissue damage and autoimmunity. Aberrant NET formation can therefore contribute to autoimmune diseases and excessive inflammation, as seen in conditions like rheumatoid arthritis. In the context of gene-specific activation, citrullination of histone H3 at arginine 2 (H3R2) is associated with active gene promoters. This modification can disrupt the binding of repressive factors, facilitating the recruitment of transcriptional activators and RNA polymerase II to promote gene expression. Citrullination can also contribute to global transcriptional activation. For instance, citrullination of histone H3 at arginine 26 (H3R26) has been associated with global transcriptional activation in response to certain cellular signals, such as growth factors or immune stimulation. Explore our full arginine deiminase product range below and discover more, for less.