{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:33:39Z","timestamp":1772156019175,"version":"3.50.1"},"reference-count":40,"publisher":"The Royal Society","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100002729","name":"Anhui University","doi-asserted-by":"crossref","award":["Y040418157"],"award-info":[{"award-number":["Y040418157"]}],"id":[{"id":"10.13039\/501100002729","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32071158"],"award-info":[{"award-number":["32071158"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation","award":["1608085MH212"],"award-info":[{"award-number":["1608085MH212"]}]},{"name":"Natural Science Foundation","award":["2008085MC68"],"award-info":[{"award-number":["2008085MC68"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>\n                    Bipolar disorder (BPD) is a psychiatric disorder characterized by alternate episodes of mania and depression. Disruption of normal circadian clock and abnormal sleep cycles are common symptoms of BPD patients. Lithium salt is currently an effective clinical therapeutic drug for BPD. Animal and cellular studies have found that lithium salt can upregulate the expression of the clock gene\n                    <jats:italic>Per2<\/jats:italic>\n                    , but the mechanism is unknown. We aim to understand the mechanism underlying the\n                    <jats:italic>Per2<\/jats:italic>\n                    upregulation by lithium treatment. By taking approaches of both comparative transcriptome analysis and comparative qPCR analysis between human and murine cells, Lumicycle assay, luciferase assay and RT-qPCR assay showed that lithium could significantly upregulate the expression of\n                    <jats:italic>Per2<\/jats:italic>\n                    in both mouse and human cells, and significantly inhibit the expression of\n                    <jats:italic>E4bp4<\/jats:italic>\n                    , which encodes a transcriptional inhibitor of\n                    <jats:italic>Per2<\/jats:italic>\n                    . After knocking out the cis-element upstream on the\n                    <jats:italic>Per2<\/jats:italic>\n                    promoter that responds to E4BP4, the upregulation effect on\n                    <jats:italic>Per2<\/jats:italic>\n                    by lithium disappeared. When\n                    <jats:italic>E4bp4<\/jats:italic>\n                    gene was knocked out, the upregulation effect on\n                    <jats:italic>Per2<\/jats:italic>\n                    by lithium salt disappeared. This study has found that lithium upregulates\n                    <jats:italic>Per2<\/jats:italic>\n                    expression by reducing the expression of transcription factor E4BP4, but the mechanism of lithium salt downregulation of E4BP4 remains to be further studied. Our study provides a new therapeutic target and approaches for treating BPD.\n                  <\/jats:p>","DOI":"10.1098\/rsob.210140","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T19:05:41Z","timestamp":1639508741000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative transcriptome analysis and CRISPR\/Cas9 gene editing reveal that E4BP4 mediates lithium upregulation of\n                    <i>Per2<\/i>\n                    expression"],"prefix":"10.1098","volume":"11","author":[{"given":"Qin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kankan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiameng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Modern Experiment Technology Center, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-2434","authenticated-orcid":true,"given":"Ximing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui Province 230601, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.5.543"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00843.x"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12270"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.05.007"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12514"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81014-4"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.02.018"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00825-5"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.07.018"},{"key":"e_1_3_6_11_2","first-page":"1122","article-title":"Genetic and epigenetic regulations of mammalian circadian rhythms","volume":"39","author":"Yue M","year":"2017","unstructured":"Yue M, Yang Y, Guo GL, Qin XM. 2017 Genetic and epigenetic regulations of mammalian circadian rhythms. 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