NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils

Yanfang Peipei Zhu; Mary Speir; Zhe Hao Tan; Jamie Casey Lee; Cameron J. Nowell; Alyce A. Chen; Hajera Amatullah; Ari J. Salinger; Carolyn J. Huang; Gio Wu; Weiqi Peng; Kasra Askari; Eric Griffis; Majid Ghassemian; Jennifer Santini; Motti Gerlic; William B. Kiosses; Sergio D. Catz; Hal M. Hoffman; Kimberly F. Greco; Edie Weller; Paul R. Thompson; Lai Ping Wong; Ruslan Sadreyev; Kate L. Jeffrey; Ben A. Croker

doi:10.1126/sciadv.adj1397

NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils

Yanfang Peipei Zhu, Mary Speir, Zhe Hao Tan, Jamie Casey Lee, Cameron J. Nowell, Alyce A. Chen, Hajera Amatullah, Ari J. Salinger, Carolyn J. Huang, Gio Wu, Weiqi Peng, Kasra Askari, Eric Griffis, Majid Ghassemian, Jennifer Santini, Motti Gerlic, William B. Kiosses, Sergio D. Catz, Hal M. Hoffman, Kimberly F. GrecoEdie Weller, Paul R. Thompson, Lai Ping Wong, Ruslan Sadreyev, Kate L. Jeffrey, Ben A. Croker

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

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Abstract

Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor–mediated apoptosis promote gasdermin E (GSDME)–dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.

Original language	English (US)
Article number	eadj1397
Journal	Science Advances
Volume	9
Issue number	51
DOIs	https://doi.org/10.1126/sciadv.adj1397
State	Published - Dec 2023

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Zhu, Y. P., Speir, M., Tan, Z. H., Lee, J. C., Nowell, C. J., Chen, A. A., Amatullah, H., Salinger, A. J., Huang, C. J., Wu, G., Peng, W., Askari, K., Griffis, E., Ghassemian, M., Santini, J., Gerlic, M., Kiosses, W. B., Catz, S. D., Hoffman, H. M., ... Croker, B. A. (2023). NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils. Science Advances, 9(51), Article eadj1397. https://doi.org/10.1126/sciadv.adj1397

Zhu, YP, Speir, M, Tan, ZH, Lee, JC, Nowell, CJ, Chen, AA, Amatullah, H, Salinger, AJ, Huang, CJ, Wu, G, Peng, W, Askari, K, Griffis, E, Ghassemian, M, Santini, J, Gerlic, M, Kiosses, WB, Catz, SD, Hoffman, HM, Greco, KF, Weller, E, Thompson, PR, Wong, LP, Sadreyev, R, Jeffrey, KL & Croker, BA 2023, 'NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils', Science Advances, vol. 9, no. 51, eadj1397. https://doi.org/10.1126/sciadv.adj1397

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title = "NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils",

abstract = "Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor–mediated apoptosis promote gasdermin E (GSDME)–dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.",

author = "Zhu, {Yanfang Peipei} and Mary Speir and Tan, {Zhe Hao} and Lee, {Jamie Casey} and Nowell, {Cameron J.} and Chen, {Alyce A.} and Hajera Amatullah and Salinger, {Ari J.} and Huang, {Carolyn J.} and Gio Wu and Weiqi Peng and Kasra Askari and Eric Griffis and Majid Ghassemian and Jennifer Santini and Motti Gerlic and Kiosses, {William B.} and Catz, {Sergio D.} and Hoffman, {Hal M.} and Greco, {Kimberly F.} and Edie Weller and Thompson, {Paul R.} and Wong, {Lai Ping} and Ruslan Sadreyev and Jeffrey, {Kate L.} and Croker, {Ben A.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

month = dec,

doi = "10.1126/sciadv.adj1397",

language = "English (US)",

volume = "9",

journal = "Science Advances",

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T1 - NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils

AU - Zhu, Yanfang Peipei

AU - Speir, Mary

AU - Tan, Zhe Hao

AU - Lee, Jamie Casey

AU - Nowell, Cameron J.

AU - Chen, Alyce A.

AU - Amatullah, Hajera

AU - Salinger, Ari J.

AU - Huang, Carolyn J.

AU - Wu, Gio

AU - Peng, Weiqi

AU - Askari, Kasra

AU - Griffis, Eric

AU - Ghassemian, Majid

AU - Santini, Jennifer

AU - Gerlic, Motti

AU - Kiosses, William B.

AU - Catz, Sergio D.

AU - Hoffman, Hal M.

AU - Greco, Kimberly F.

AU - Weller, Edie

AU - Thompson, Paul R.

AU - Wong, Lai Ping

AU - Sadreyev, Ruslan

AU - Jeffrey, Kate L.

AU - Croker, Ben A.

PY - 2023/12

Y1 - 2023/12

N2 - Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor–mediated apoptosis promote gasdermin E (GSDME)–dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.

AB - Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor–mediated apoptosis promote gasdermin E (GSDME)–dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.

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NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils

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