Skip to main content
Article thumbnail
Location of Repository

Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

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


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

Topics: Research Articles
Publisher: The Rockefeller University Press
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2006). An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps.
  2. (2005). Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells.
  3. (2005). Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils.
  4. (2007). Chromatin modifi cations and their function.
  5. (2006). Complex of linker histone H5 with the nucleosome and its implications for chromatin packing.
  6. (2002). Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes.
  7. (2006). DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps.
  8. (2004). Histone deimination antagonizes arginine methylation.
  9. (2006). Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization.
  10. (2006). Macromolecular size-and-shape distributions by sedimentation velocity analytical ultracentrifugation.
  11. (2004). Neutrophil extracellular traps kill bacteria.
  12. (2007). Novel cell death program leads to neutrophil extracellular traps.
  13. (2008). Regulation of p53 target gene expression by peptidylarginine deiminase 4.
  14. (2007). The H3 tail domain participates in multiple interactions during folding and self-association of nucleosome arrays.
  15. (2007). The role of chromatin during transcription.
  16. (2001). Translating the histone code.
  17. (1999). Twenty-fi ve years of the nucleosome, fundamental particle of the eukaryote chromosome.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.