{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:40:11Z","timestamp":1793331611954,"version":"4.5.0"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8217111397"],"award-info":[{"award-number":["8217111397"]}],"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":["32525019"],"award-info":[{"award-number":["32525019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110272"],"award-info":[{"award-number":["2022A1515110272"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Grants Council Hong Kong Project","award":["14104223"],"award-info":[{"award-number":["14104223"]}]},{"name":"Research Grants Council Hong Kong Project","award":["R4007-23"],"award-info":[{"award-number":["R4007-23"]}]},{"name":"Research Grants Council Hong Kong Project","award":["11105623"],"award-info":[{"award-number":["11105623"]}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["32570682"],"award-info":[{"award-number":["32570682"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:p>\n                    Cancer progression is driven by the accumulation of DNA mutations and aberrant gene regulation. Recent studies have demonstrated that multiple H3 mutations serve as drivers of tumorigenesis. However, the role and significance of various cancer-associated histone H2B mutations in cancer development remain unknown. Here, we investigate H2BE113K, a missense mutation of histone H2B predominantly found in patients with breast cancer. We show that H2BE113K promotes colony formation in breast cancer. Notably, transcriptomic analysis reveals differential expression of genes in various cancer pathways in H2BE113K cells. The loci with elevated gene expression display increased chromatin accessibility, accompanied by H2BE113K enrichment. Depletion of\n                    <jats:italic toggle=\"yes\">G3BP2<\/jats:italic>\n                    , one of the H2BE113K target genes that has been implicated in breast cancer, reduces the colony formation phenotype in H2BE113K cells. In addition, H2BE113K knock-in mice crossbred with an MMTV-PyMT breast cancer model show elevated lung metastasis. Together, our findings provide critical insights in the mechanistic role of H2BE113K in gene regulation, chromatin function, and breast cancer progression.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx4982","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:37Z","timestamp":1783706317000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0939-2130","authenticated-orcid":true,"given":"Shiman","family":"Hu (\u80e1\u8bd7\u66fc)","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4198-6706","authenticated-orcid":true,"given":"Jiaxian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."},{"name":"Institute of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, the First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-8914","authenticated-orcid":true,"given":"Jiaqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-8341","authenticated-orcid":true,"given":"Jiaohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-180X","authenticated-orcid":true,"given":"Tiantian","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-3336","authenticated-orcid":true,"given":"Yi Ching Esther","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-8034","authenticated-orcid":true,"given":"Xiaoxuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuting","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-9266","authenticated-orcid":true,"given":"Yabin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-8698","authenticated-orcid":true,"given":"Junhong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2460-4808","authenticated-orcid":true,"given":"Hoi Leong Xavier","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-1379","authenticated-orcid":true,"given":"Robert S.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9295-1951","authenticated-orcid":true,"given":"Haojie","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-8483","authenticated-orcid":true,"given":"Mo","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, School of Basic Sciences, Tsinghua University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0251-9159","authenticated-orcid":true,"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-1031","authenticated-orcid":true,"given":"Yogen","family":"Saunthararajah","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0293-8778","authenticated-orcid":true,"given":"Haiyun","family":"Gan","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6430-3340","authenticated-orcid":true,"given":"Kui Ming","family":"Chan (\u9648\u5c45\u660e)","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong SAR, China."},{"name":"Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.1.245"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/38444"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1038-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0393"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1102"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10833"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232245"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.217778.113"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3757"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2814"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-7-29"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.25625"},{"key":"e_1_3_2_15_2","first-page":"694","article-title":"Histone H2B mutations in cancer","volume":"9","author":"Wan Y. C. E.","year":"2021","unstructured":"Y. C. E. Wan, K. M. Chan, Histone H2B mutations in cancer. Biomedicine 9, 694 (2021).","journal-title":"Biomedicine"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00219-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-0131-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100374"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116596"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.10.023"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2012.1022"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-37633-X_2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2012.04.001"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2015.11.014"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.044"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2087-1"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.35322"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23671"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46057"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes6020299"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.166929"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.7.1819-1826.2002"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.062706.153223"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/19491034.2016.1211217"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80797-7"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80796-5"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.14.3781"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00738-1"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0413-4"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174287"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00009-09"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005420"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12915"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525387114"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-119311"},{"key":"e_1_3_2_46_2","first-page":"5913","article-title":"Silencing of semaphorin 3C suppresses cell proliferation and migration in MCF-7 breast cancer cells","volume":"14","author":"Zhu X.","year":"2017","unstructured":"X. Zhu, X. Zhang, Z. Ye, Y. Chen, L. Lv, X. Zhang, H. Hu, Silencing of semaphorin 3C suppresses cell proliferation and migration in MCF-7 breast cancer cells. Oncol. Lett. 14, 5913\u20135917 (2017).","journal-title":"Oncol. Lett."},{"key":"e_1_3_2_47_2","first-page":"1281","article-title":"Expression of semaphorin 3C in breast cancer and its impact on adhesion and invasion of breast cancer cells","volume":"36","author":"Malik M. F.","year":"2016","unstructured":"M. F. Malik, L. K. Satherley, E. L. Davies, L. Ye, W. G. Jiang, Expression of semaphorin 3C in breast cancer and its impact on adhesion and invasion of breast cancer cells. Anticancer Res 36, 1281\u20131286 (2016).","journal-title":"Anticancer Res"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-11-r125"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2563"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.052"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.022"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.035"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.033"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90216-3"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1032202"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1115-5"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21856"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4396"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb2129s109"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.018"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1112s47"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty648"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx4982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:58Z","timestamp":1783706338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx4982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":66,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2026,7,10]]}},"alternative-id":["10.1126\/sciadv.adx4982"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adx4982","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx4982"}}