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However, the oncogenic transformation determined by\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    in vivo and its impact on chromatin dynamics are incompletely understood. Here, we generate a transgenic mouse model with doxycycline-inducible expression of human\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    in the context of the MMTV-PyMT breast cancer-prone background to systematically interrogate the cellular mechanisms by which human\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    lncRNA acts to promote breast cancer progression. We show that sustained high levels of\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    over time increased breast metastatic capacity and invasiveness in breast cancer cells, promoting migration and subsequent metastasis to the lung. Subsequent withdrawal of\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    overexpression reverted the metastatic phenotype, indicating oncogenic lncRNA addiction. Furthermore,\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted EMT. These alterations are abrogated within several cell cycles after\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    in programming a metastatic gene regulatory program. Targeting\n                    <jats:italic>HOTAIR<\/jats:italic>\n                    lncRNA may potentially serve as a therapeutic strategy to ameliorate breast cancer progression.\n                  <\/jats:p>","DOI":"10.7554\/elife.79126","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T08:00:19Z","timestamp":1672300819000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.79126","source":"Crossref","is-referenced-by-count":32,"title":["Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-5275","authenticated-orcid":true,"given":"Qing","family":"Ma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5405-6411","authenticated-orcid":true,"given":"Liuyi","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Tolentino","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine","place":["Stanford, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine","place":["Stanford, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Personal Dynamic 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