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Accumulating strong evidence indicates that genetic factors contribute to NTDs etiology, among them,\u00a0<jats:italic>HOX<\/jats:italic> genes play a key role in neural tube closure. Although abnormal <jats:italic>HOX<\/jats:italic> gene expression can lead to NTDs, the underlying pathological mechanisms have not fully been understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>We detected that H3K27me3 and expression of the <jats:italic>Hox<\/jats:italic> genes in a retinoic acid (RA) induced mouse NTDs model on E8.5, E9.5 and E10.5 using RNA-sequencing and chromatin immunoprecipitation sequencing\u00a0assays. Furthermore, we quantified 10 <jats:italic>Hox<\/jats:italic> genes using NanoString nCounter in brain tissue of fetuses with 39 NTDs patients including anencephaly, spina bifida, hydrocephaly and encephalocele.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, our results showed differential expression in 26 genes with a &gt;\u200920-fold change in the level of expression, including 10 upregulated <jats:italic>Hox<\/jats:italic> genes. RT-qPCR revealed that these 10 <jats:italic>Hox<\/jats:italic> genes were all upregulated in RA-induced mouse NTDs as well as RA-treated embryonic stem cells (ESCs). Using ChIP-seq assays, we demonstrate that a decrease in H3K27me3 level upregulates the expression of <jats:italic>Hox<\/jats:italic> cluster <jats:italic>A\u2013D<\/jats:italic> in RA-induced mouse NTDs model on E10.5. Interestingly, RA treatment led to attenuation of H3K27me3 due to cooperate between UTX and Suz12, affecting <jats:italic>Hox<\/jats:italic> gene regulation. Further analysis, in human anencephaly cases, upregulation of 10 <jats:italic>HOX<\/jats:italic> genes was observed, along with aberrant levels of H3K27me3. Notably, <jats:italic>HOXB4<\/jats:italic>, <jats:italic>HOX<\/jats:italic>C4 and <jats:italic>HOX<\/jats:italic>D1 expression was negatively correlated with H3K27me3 levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results indicate that abnormal <jats:italic>HOX<\/jats:italic> gene expression induced by aberrant H3K27me3 levels may be a risk factor for NTDs and highlight the need for further analysis of genome-wide epigenetic modification in NTDs.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13072-019-0318-1","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T09:04:20Z","timestamp":1576746260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Reduced H3K27me3 leads to abnormal Hox gene expression in neural tube defects"],"prefix":"10.1186","volume":"12","author":[{"given":"Juan","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifang","family":"Ao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"318_CR1","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1023\/A:1020977409850","volume":"27","author":"RH Finnell","year":"2002","unstructured":"Finnell RH, Junker WM, Wadman LK, Cabrera RM. 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