Histone H3 (Citrullinated R2+R8+R17+R26) Monoclonal Antibody (Clone 7A4E11)

Histone H3 is a nuclear protein and a component of the nucleosome core that is essential for organizing genomic DNA in eukaryotic nuclei.¹ It is a globular protein that contains an unstructured N-terminal tail that extends outside of the nucleosome core and is subject to various post-translational modifications, including citrullination. Histone H3 is subject to citrullination of arginine residues by peptidyl arginine deiminase 2 (PAD2) and PAD4 at positions 2, 8, 17, and 26, and this citrullination blocks methylation of these residues by protein-arginine methyltransferase 4 (PRMT4) and modulates the transcription of target genes. Citrullinated histone H3 is a component of neutrophil extracellular traps (NETs) that acts as an autoantigen to induce the production of anti-citrullinated protein antibodies associated with various diseases such as sepsis, multiple sclerosis, rheumatoid arthritis, and multiple myeloma.^1,2,3,4 Increased serum levels of histone H3 citrullinated at R2, R8, and R17 have been found in patients with asthma and in septic shock patients where they are positively associated with a sequential organ failure assessment (SOFA) score and poor survival.^5,6 Citrullination of histone H3 at R26 can be induced by estradiol (Item No. 10006315) and activates transcription mediated by estrogen receptor α (ERα) in ER-positive breast cancers in vitro.⁷ Cayman's Histone H3 (citrullinated R2 + R8 + R17 + R26) Monoclonal Antibody can be used for ELISA and Western Blot (WB) and as a neutralizing antibody. This antibody recognizes citrullinated histone H3 (R2 + R8 + R17 + R26) at approximately 15.5 kDa.

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1. Xu, Y.-M., Du, J.-Y., and Lau, A.T.Y. Posttranslational modifications of human histone H3: An update. Proteomics 14(17-18), 2047-2060 (2014).

2. Li, Y., Liu, Z., Liu, B., et al. Citrullinated histone H3: A novel target for the treatment of sepsis. Surgery 156(2), 229-234 (2014).

3. Moscarello, M.A., Mastronardi, F.G., and Wood, D.D. The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis. Neurochem. Res. 32(2), 251-256 (2007).

4. McNee, G., Eales, K.L., Wei, W., et al. Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma. Leukemia 31(2), 373-381 (2017).

5. Kuczia, P., Zuk, J., Iwaniec, T., et al. Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients. Clin. Transl. Allergy 10, 31 (2020).

6. Tian, Y., Russo, R.M., Li, Y., et al. Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity. Infection 49(1), 83-93 (2021).

7. Zhang, X., Bolt, M., Guertin, M.J., et al. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation. Proc. Natl. Acad. Sci. USA 109(33), 13331-13336 (2012).