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However, the molecular mechanisms underlying the coupling of signal transduction and gene activation through condensate formation, and how dysregulation of these mechanisms contributes to disease progression, remain elusive. Here, the authors report that CREB\u2010regulated transcription coactivator 2 (CRTC2) translocates to the nucleus and forms phase\u2010separated condensates upon activation of cAMP signaling. They show that intranuclear CRTC2 interacts with positive transcription elongation factor b (P\u2010TEFb) and activates P\u2010TEFb by disrupting the inhibitory 7SK snRNP complex. Aberrantly elevated cAMP signaling plays central roles in the development of autosomal dominant polycystic kidney disease (ADPKD). They find that CRTC2 localizes to the nucleus and forms condensates in cystic epithelial cells of both mouse and human ADPKD kidneys. Genetic depletion of CRTC2 suppresses cyst growth in an orthologous ADPKD mouse model. Using integrative transcriptomic and cistromic analyses, they identify CRTC2\u2010regulated cystogenesis\u2010associated genes, whose activation depends on CRTC2 condensate\u2010facilitated P\u2010TEFb recruitment and the release of paused RNA polymerase II. Together, their findings elucidate a mechanism by which CRTC2 nuclear condensation conveys cAMP signaling to transcription elongation activation and thereby promotes cystogenesis in ADPKD.<\/jats:p>","DOI":"10.1002\/advs.202104578","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T05:32:42Z","timestamp":1642397562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["cAMP\u2010Induced Nuclear Condensation of CRTC2 Promotes Transcription Elongation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1002","volume":"9","author":[{"given":"Zeyun","family":"Mi","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co\u2010sponsored Collaborative Innovation Center for Medical Epigenetics Department of Biochemistry and Molecular Biology School of Basic Medical 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