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Mitochondrial- and death receptor\u2013mediated apoptosis promote gasdermin E (GSDME)\u2013dependent 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.<\/jats:p>","DOI":"10.1126\/sciadv.adj1397","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T13:58:40Z","timestamp":1703080720000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":88,"title":["NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-0860","authenticated-orcid":true,"given":"Yanfang Peipei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA."},{"name":"Immunology Center of Georgia, Augusta University, Augusta, GA 30912, 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