Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

Yanming Wang, Ming Li, Sonja Stadler, Sarah Correll, Pingxin Li, Danchen Wang, Ryo Hayama, Lauriebeth Leonelli, Hyunsil Han, Sergei A. Grigoryev, C. David Allis, Scott A. Coonrod

Research output: Contribution to journalArticle

649 Scopus citations

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 defi ned 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.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalJournal of Cell Biology
Volume184
Issue number2
DOIs
StatePublished - Jan 26 2009

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint Dive into the research topics of 'Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation'. Together they form a unique fingerprint.

  • Cite this

    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, 184(2), 205-213. https://doi.org/10.1083/jcb.200806072