{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:05:12Z","timestamp":1789538712392,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory gene programs must be precisely controlled to maintain immune homeostasis, yet the chromatin mechanisms enforcing transcriptional shutdown remain unclear. Here we show that the histone variant H2A.Z is evicted from pro-inflammatory loci upon acute macrophage activation and re-deposited during resolution. Myeloid-specific H2a.z deletion in mice causes unrestrained inflammatory transcription, arrested macrophage maturation, exacerbates colitis and dysbiosis, depleting butyrate-producing bacteria. Consistently, gut short-chain fatty acids, particularly butyrate, promote H2A.Z deposition through histone acylation, and butyrate's anti-inflammatory effects require H2A.Z. Strikingly, human inflammatory bowel disease (IBD)-associated risk variants are linked to reduced expression of GAS41 and TIP60, which form a reader-writer module that senses acylation mark to direct H2A.Z deposition. Diminished GAS41\/TIP60 expression in patient tissues correlates with IBD progression and poor response to anti-TNF therapy. Thus, H2A.Z deposition functions as an acylation-dependent epigenetic checkpoint that couples macrophage differentiation to inflammatory resolution, integrating host genetics and microbial metabolites to calibrate immune responses.<\/jats:p>","DOI":"10.1093\/procel\/pwag069","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:22:23Z","timestamp":1789384943000},"source":"Crossref","is-referenced-by-count":0,"title":["An H2A.Z-dependent epigenetic checkpoint in macrophages couples genetic risk to microbial metabolite signaling"],"prefix":"10.1093","author":[{"given":"Zhaoran","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyi","family":"Meng","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Digestive Diseases Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, , Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjian","family":"Piao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiao","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyu","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Department of Preventive and Pediatric Dentistry, , Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqin","family":"Jia","sequence":"additional","affiliation":[{"name":"Tianjin Medical University National Demonstration Center for Experimental Basic Medical Science Education, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyu","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Hospital of Tianjin Medical University Department of Emergency Medicine, , Tianjin 300211,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Cao","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Digestive Diseases Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, , Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"The Province and Ministry Co , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Medical University , -sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, , Department of Cell Biology, School of Basic Medical Sciences, , Tianjin 300070,","place":["China"]},{"name":"Tianjin Institute of Digestive Diseases Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, , Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"container-title":["Protein &amp; Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article-pdf\/doi\/10.1093\/procel\/pwag069\/71103856\/pwag069.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article-pdf\/doi\/10.1093\/procel\/pwag069\/71103856\/pwag069.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:36:32Z","timestamp":1789536992000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article\/doi\/10.1093\/procel\/pwag069\/8799010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/procel\/pwag069","relation":{},"ISSN":["1674-800X","1674-8018"],"issn-type":[{"value":"1674-800X","type":"print"},{"value":"1674-8018","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"pwag069"}}