title: β-Arrestin1/miR-326 Transcription Unit Is Epigenetically Regulated in Neural Stem Cells Where It Controls Stemness and Growth Arrest.
abstract: Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host geneβ-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells. Such a regulation is mediated by CpG islands methylation of the common promoter. Epigenetic derepression ofβ-arrestin1/miR-326 by differentiation signals or demethylating agents leads to suppression of stemness features and cell growth and promotes cell differentiation.β-Arrestin1 inhibits cell proliferation by enhancing the nuclear expression of the cyclin-dependent kinase inhibitor p27. Therefore, we propose a new mechanism for the control of cerebellar NSCs where a coordinated epigenetic mechanism finely regulatesβ-arrestin1/miR-326 expression and consequently NSCs stemness and cell growth.
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Agnese
authors.identifier: 0000-0002-9346-8782
authors.initials: A
authors.lastname: Po
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Begalli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Abballe
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.identifier: 0000-0001-8594-9837
authors.initials: V
authors.lastname: Alfano
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Zein Mersini
authors.identifier: 0000-0003-0317-9854
authors.initials: ZM
authors.lastname: Besharat
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catanzaro
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vacca
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tafani
authors.affiliation: Department of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Elisabetta
authors.identifier: 0000-0001-7265-6429
authors.initials: E
authors.lastname: Ferretti
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Evelina
authors.identifier: 0000-0002-4747-1032
authors.initials: E
authors.lastname: Miele