Histone H3 is one of the five main histones involved in the structure of chromatin. H3 has a main globular domain and a long N-terminal tail, and is critical to maintaining the structure of the 'beads on a string' structure of nucleosomes. Histones are subject to various modifications, including phosphorylation, acetylation, glycosylation, methylation, ubiquitination and citrullination. The N-terminus of H3 protrudes from the globular nucleosome core and is susceptible to post-translational modification. In fact, of the five histones, histone H3 is the one that undergoes the most extensive post-transcriptional modifications. The term “Histone H3” does not distinguish between sequence variants or modification state which play a large role in the dynamics and long-term regulation of genes. Histone H3 is an important protein in the emerging field of epigenetics, where its sequence variants and post-translational modifications play a role in the dynamic and long-term regulation of genes.
Histone citrullination, a posttranscriptional modification catalyzed by peptidyl arginine deiminase (PAD) enzymes, is involved in the formation of neutrophil extracellular traps (NETs) — a unique form of cell death that neutrophils undergo — and in human carcinogenesis. NETs help neutralize pathogens and restore homeostasis. However, uncontrolled NET formation (NETosis) is involved in multiple diseases. Citrullinated histone H3 is a NET-specific biomarker.
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