{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:28:22Z","timestamp":1788449302460,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471163"],"award-info":[{"award-number":["81471163"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771584"],"award-info":[{"award-number":["81771584"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,8,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Maternal diabetes related neural tube defects (NTDs) are a result of oxidative stress and apoptosis. However, the molecular mechanism behind the pathogenesis is not fully understood. Here, we report that high glucose exposure\u2010induced epigenetic changes influence histone H4 acetylation and neuroepithelial cell proliferation. We also show that the acetyltransferase inhibitor C646 can prevent high glucose induced changes in histone H4 acetylation and neuroepithelial cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By using LC\u2010MS\/MS as an unbiased approach, we screened the histone acetylation profile in an E9 neuroepithelial cell line (NE\u20104C) under high glucose exposure. We further explored the mechanism in cells <jats:italic>in vitro<\/jats:italic> and in maternal diabetes\u2010induced mouse embryos <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 35 core histone acetylation marks in normal E9 neuroepithelial cells, whereas high glucose exposure resulted in novel acetylation sites on H4K31 and H4K44. Acetylation levels of embryonic development associated H4K5\/K8\/K12\/K16 increased in neuroepithelial cells exposed to high glucose <jats:italic>in vitro<\/jats:italic> and in brain tissue from maternal diabetes induced exencephalic embryos <jats:italic>in vivo<\/jats:italic>. Further, mRNA level of histone acetyltransferase CBP encoded gene <jats:italic>Crebbp<\/jats:italic> was significantly increased both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The addition of C646, a selective inhibitor for CBP\/p300, significantly rescued increase of H4K5\/K8\/K12\/K16 acetylation levels and H3S10pi\u2010labeled neuroepithelial cell proliferation induced by high glucose exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data provide complementary insights for potential mechanisms of maternal diabetes induced NTDs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1360","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T16:10:16Z","timestamp":1534435816000},"page":"1118-1128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["CBP\/p300 inhibitor C646 prevents high glucose exposure induced neuroepithelial cell proliferation"],"prefix":"10.1002","volume":"110","author":[{"given":"Baoling","family":"Bai","sequence":"first","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing 100020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing 100020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Wan","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing 100020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing 100020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key 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