{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:47:12Z","timestamp":1791917232005,"version":"4.3.4"},"reference-count":0,"publisher":"Cold Spring Harbor Laboratory","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genome Res."],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"\n Some long noncoding RNAs (lncRNAs) are known to regulate gene expression. However, the underlying temporal dynamics of lncRNAs influencing gene and epigenetic regulation, as well as mechanisms of lncRNA regulation in\n trans<\/jats:italic>\n , are less understood. To investigate this, we genetically engineer 17 doxycycline-inducible lncRNA transgenes for ectopic expression at the\n H11<\/jats:italic>\n safe harbor locus in human pluripotent stem cells (hiPSCs), and we generate high-density temporal RNA-seq and ATAC-seq profiles. Most lncRNA transgenes are induced at 2 h and maintain expression through the 96 h time course. Surprisingly, when we seek to identify gene expression changes owing to the lncRNAs, we find that the global transcriptional landscape is dominated by a strong systemic response triggered by doxycycline exposure. We rigorously define this cohort of genes as a doxycycline-responsive gene signature (DRGS). The DRGS is also present in at least 28 public data sets from dox-inducible transgene studies involving diverse cell types. Next, we determine which lncRNAs exhibit\n trans<\/jats:italic>\n -regulatory events. We identify\n DANCR<\/jats:italic>\n ,\n FENDRR<\/jats:italic>\n ,\n LINC00667<\/jats:italic>\n ,\n LINC00847<\/jats:italic>\n ,\n LNCPRESS1<\/jats:italic>\n , and\n LNCPNKY<\/jats:italic>\n as lncRNAs that regulate specific transcript expression in\n trans<\/jats:italic>\n . The downstream target genes encode 53 mRNAs and 10 lncRNAs. None of the target lncRNAs alter gene expression proximal to their own loci (i.e., triggering secondary\n cis<\/jats:italic>\n -effects). Surprisingly, the target genes of\n LINC00847<\/jats:italic>\n (transcribed from Chromosome 22) are substantially enriched on Chromosome 19, with a preponderance of target genes encoding RNA metabolism and RNA splicing factors. Collectively, our study provides a resource to discern artifacts in the doxycycline-inducible system and identifies temporally regulated targets of six lncRNAs for future mechanistic studies.\n <\/jats:p>","DOI":"10.1101\/gr.282389.126","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:10:17Z","timestamp":1791562217000},"source":"Crossref","is-referenced-by-count":0,"title":["Temporal transcriptomics identifies\n trans<\/i>\n -regulation by multiple lncRNAs in human iPSCs"],"prefix":"10.1101","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9011-3531","authenticated-orcid":false,"given":"Mingfeng","family":"Liu","sequence":"first","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"},{"name":"Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado 80302, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0707-5588","authenticated-orcid":false,"given":"Izabela","family":"Mamede","sequence":"additional","affiliation":[{"name":"Pioneer Science Initiative, D'Or Institute for Research and Education (IDOR), S\u00e3o Paulo, S\u00e3o Paulo 01401-002, Brazil;"},{"name":"Laboratory of Bioinformatics and Computational Biology, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Rio de Janeiro, 20231-050, Brazil;"},{"name":"Laboratory of Genetics Biochemistry, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-1694","authenticated-orcid":false,"given":"Sajad","family":"Sofi","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-9965","authenticated-orcid":false,"given":"Isabela T.","family":"Pereira","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-8558","authenticated-orcid":false,"given":"Vishantie","family":"Dostal","sequence":"additional","affiliation":[{"name":"LincSwitch Therapeutics, Incorporated, Boulder, Colorado 80302, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7072-5603","authenticated-orcid":false,"given":"Alison R.S.","family":"Pashos","sequence":"additional","affiliation":[{"name":"LincSwitch Therapeutics, Incorporated, Boulder, Colorado 80302, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"McMahon","sequence":"additional","affiliation":[{"name":"LincSwitch Therapeutics, Incorporated, Boulder, Colorado 80302, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneesh","family":"Waikar","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado 80302, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Stephenson","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7338-3389","authenticated-orcid":false,"given":"Thomas R.","family":"Cech","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"},{"name":"Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-7539","authenticated-orcid":false,"given":"John L.","family":"Rinn","sequence":"additional","affiliation":[{"name":"BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado 80303, USA;"},{"name":"LincSwitch Therapeutics, Incorporated, Boulder, Colorado 80302, USA;"},{"name":"Department of Biochemistry, University of Colorado Boulder, Boulder, Colorado 80303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,10,9]]},"container-title":["Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gr.282389.126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:10:19Z","timestamp":1791915019000},"score":1,"resource":{"primary":{"URL":"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.282389.126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":0,"alternative-id":["10.1101\/gr.282389.126"],"URL":"https:\/\/doi.org\/10.1101\/gr.282389.126","relation":{},"ISSN":["1088-9051","1549-5469"],"issn-type":[{"value":"1088-9051","type":"print"},{"value":"1549-5469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]}}}