Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

2009/01/19 by Yanming Wang, Ming Li, Sonja C. Stadler +10 · 1,499 citations
Immunology and Microbiology · #Biochemistry #Biology #Cell biology #Chromatin #Citrullination #Citrulline #DNA #Histone #Histone H1 #Histone H2A #Histone code #Histone octamer #Immune Response and Inflammation #Immune cells in cancer #Immunology #Inflammation #Molecular biology #Neutrophil extracellular traps #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Nucleosome

paper · pdf · doi:10.1083/jcb.200806072

published in The Journal of Cell Biology 184(2), 205-213 (Rockefeller University Press)

openalex publication_date 2009/01/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/02

Abstract

Peripheral blood neutrophils form highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs), that have been implicated in innate immune response to bacterial infection. Neutrophils express high levels of peptidylarginine deiminase 4 (PAD4), which catalyzes histone citrullination. However, whether PAD4 or histone citrullination plays a role in chromatin structure in neutrophils is unclear. In this study, we show that the hypercitrullination of histones by PAD4 mediates chromatin decondensation. Histone hypercitrullination is detected on highly decondensed chromatin in HL-60 granulocytes and blood neutrophils. The inhibition of PAD4 decreases histone hypercitrullination and the formation of NET-like structures, whereas PAD4 treatment of HL-60 cells facilitates these processes. The loss of heterochromatin and multilobular nuclear structures is detected in HL-60 granulocytes after PAD4 activation. Importantly, citrullination of biochemically defined avian nucleosome arrays inhibits their compaction by the linker histone H5 to form higher order chromatin structures. Together, these results suggest that histone hypercitrullination has important functions in chromatin decondensation in granulocytes/neutrophils.

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