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Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

Open access
Wang, Yanming, Li, Ming, Stadler, Sonja, Correll, Sarah, Li, Pingxin, Wang, Danchen, Hayama, Ryo, Leonelli, Lauriebeth, Han, Hyunsil, Grigoryev, Sergei A., Allis, C. David, Coonrod, Scott A.·2009·Journal of Cell Biology

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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Metadata

Authors
Wang, Y., Li, M., Stadler, S., Correll, S., Li, P., Wang, D., Hayama, R., Leonelli, L., Han, H., Grigoryev, S. A., Allis, C. D., & Coonrod, S. A.
Venue
Journal of Cell Biology
Published
2009-01-19
Volume
184
Issue
2
Pages
205-213
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2168176302
Cited by
1,521
References
4
FWCI
14.00
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. https://app.cochat.ai/papers/10.1083/jcb.200806072
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Wang, Y., Li, M., Stadler, S., Correll, S., Li, P., Wang, D., Hayama, R., Leonelli, L., Han, H., Grigoryev, S. A., Allis, C. D., & Coonrod, S. A. (2009). Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. Journal of Cell Biology. https://doi.org/10.1083/jcb.200806072

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