{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:05:04Z","timestamp":1787882704452,"version":"build-2784847793"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"27","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:p>\n            Down syndrome (DS) is the most common chromosomal disorder and a major cause of intellectual disability. The genetic etiology of DS is the extra copy of chromosome 21 (HSA21)\u2013encoded genes; however, the contribution of specific HSA21 genes to DS pathogenesis remains largely unknown. Here, we identified ZBTB21, an HSA21-encoded zinc-finger protein, as a transcriptional repressor in the regulation of synaptic function. We found that normalization of the\n            <jats:italic>Zbtb21<\/jats:italic>\n            gene copy number in DS mice corrected deficits in cognitive performance, synaptic function, and gene expression. Moreover, we demonstrated that ZBTB21 binds to canonical cAMP-response element (CRE) DNA and that its binding to CRE could be competitive with CRE-binding factors such as CREB. ZBTB21 represses CRE-dependent gene expression and results in the negative regulation of synaptic plasticity, learning and memory. Together, our results identify ZBTB21 as a CRE-binding protein and repressor in cAMP-dependent gene regulation, contributing to cognitive defects in DS.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adm7373","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T17:59:13Z","timestamp":1720029553000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1856-6020","authenticated-orcid":true,"given":"Muzhen","family":"Qiao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1184-6485","authenticated-orcid":true,"given":"Qianwen","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-4639","authenticated-orcid":true,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Department of Neurology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361002, China."},{"name":"Laboratory Animal Center, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5592-4487","authenticated-orcid":true,"given":"Jiahuai","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."},{"name":"Laboratory Animal Center, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."},{"name":"Research Unit of Cellular Stress of CAMS, Xiang\u2019an Hospital of Xiamen University, Cancer Research Center of Xiamen University, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm086"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80605-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0143-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30098"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200413"},{"key":"e_1_3_2_7_2","first-page":"59","article-title":"Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure","author":"Weitzdoerfer R.","year":"2001","unstructured":"R. Weitzdoerfer, M. Dierssen, M. Fountoulakis, G. Lubec, Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. J. Neural Transm. Suppl., 59\u201370 (2001).","journal-title":"J. Neural Transm. Suppl."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688755"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(83)90002-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(84)90041-4"},{"key":"e_1_3_2_11_2","first-page":"181","article-title":"Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months","volume":"9","author":"Schmidt-Sidor B.","year":"1990","unstructured":"B. Schmidt-Sidor, K. E. Wisniewski, T. H. Shepard, E. A. Sersen, Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin. Neuropathol. 9, 181\u2013190 (1990).","journal-title":"Clin. Neuropathol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90299-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00067-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.23.1.649"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/361031a0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(97)00157-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0926-6410(00)00074-4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/322419a0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2837826"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/345718a0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.186870"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/289079a0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/35085068"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39735-4"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100453"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(01)00141-0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(96)00071-5"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.11.3609-3615.2001"},{"key":"e_1_3_2_29_2","first-page":"1193","article-title":"The BTB\/POZ domain: A new protein-protein interaction motif common to DNA- and actin-binding proteins","volume":"6","author":"Albagli O.","year":"1995","unstructured":"O. Albagli, P. Dhordain, C. Deweindt, G. Lecocq, D. Leprince, The BTB\/POZ domain: A new protein-protein interaction motif common to DNA- and actin-binding proteins. Cell Growth Differ. 6, 1193\u20131198 (1995).","journal-title":"Cell Growth Differ."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.09.048"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.735795"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6448"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.147991.112"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09982-5"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114326118"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90148-1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20226"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2011.00727.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12170"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408571200"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113812"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.02.016"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813248106"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00997-9"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0697-4"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00106"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040545197"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq4515"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1317.048"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.10.1935"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.04.059"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-019-00451-z"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000525"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172308"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3120"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep21718"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2017.35"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwab024"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.09.004"},{"key":"e_1_3_2_60_2","first-page":"267","article-title":"Miniaturized GPCR signaling studies in 1536-well format","volume":"19","author":"Shultz S.","year":"2008","unstructured":"S. Shultz, T. Worzella, A. Gallagher, J. Shieh, S. Goueli, K. Hsiao, J. Vidugiriene, Miniaturized GPCR signaling studies in 1536-well format. J. Biomol. Tech. 19, 267\u2013274 (2008).","journal-title":"J. Biomol. Tech."},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165753"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adm7373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T18:00:42Z","timestamp":1720029642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adm7373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":60,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2024,7,5]]}},"alternative-id":["10.1126\/sciadv.adm7373"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adm7373","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]},"assertion":[{"value":"2023-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadm7373"}}