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However, the organization of these large genomic elements at the level of chromosome folding, beyond local enhancer-promoter interactions, remains poorly understood. Here, we report the discovery of a nuclear subcompartment in the mouse cerebellum formed by near-megabase long enhancers and their associated long genes encoding synaptic or signaling proteins. Genomic regions within this subcompartment reside in the outer-half of the nucleus, separated from other transcriptionally active structures. Using an\n                  <jats:italic>in vivo<\/jats:italic>\n                  CRISPR genetic mini-screen, we uncover a specific role for the transcription factor Etv1 in coupling the compartmentalization of neuronal long genes with their expression. Together, our study defines mechanisms that organize transcriptionally active genes across chromosomes in the mammalian brain.\n                <\/jats:p>","DOI":"10.1101\/2023.07.19.549737","type":"posted-content","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T18:30:11Z","timestamp":1689964211000},"source":"Crossref","is-referenced-by-count":6,"title":["Mega-Enhancers Compartmentalize Transcriptionally Active Long Genes in the Brain"],"prefix":"10.64898","author":[{"given":"Ziyu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar A.","family":"Pay\u00e1n Parra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichiro","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Musella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Scrutton Alvarado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Alber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025101710000695000_2023.07.19.549737v4.1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2018.10.013"},{"key":"2025101710000695000_2023.07.19.549737v4.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2014.12.004"},{"key":"2025101710000695000_2023.07.19.549737v4.3","doi-asserted-by":"crossref","first-page":"6431","DOI":"10.1007\/s00018-021-03911-w","article-title":"Transcriptome programs involved in the development and structure of the cerebellum","volume":"78","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"2025101710000695000_2023.07.19.549737v4.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.011"},{"key":"2025101710000695000_2023.07.19.549737v4.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3623"},{"key":"2025101710000695000_2023.07.19.549737v4.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2781"},{"key":"2025101710000695000_2023.07.19.549737v4.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.035"},{"key":"2025101710000695000_2023.07.19.549737v4.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.026"},{"key":"2025101710000695000_2023.07.19.549737v4.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature21411"},{"key":"2025101710000695000_2023.07.19.549737v4.10","doi-asserted-by":"crossref","unstructured":"Monahan, K. et al. 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