title: REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells.
abstract: Our previous studies have shown that the regulatory network that maintains pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context-dependent manner and can be modulated, at least in part, by re-calibration of an intracellular network of pluripotency factors as well as cues arising from the extracellular matrix. The transcriptional repressor REST represses miR-21 and, thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse embryonic fibroblast feeder cell effects. However, how miR-21 connects to the nuclear regulatory network has not been clear. Here, we show that miR-21, a direct target of REST-mediated repression, directly targets Sox2. Exogenously added miR-21 to mESCs decreases the expression of Sox2, decreasing mESC self-renewal, and this effect of miR-21 on mESC self-renewal can be blocked by expression of exogenous Sox2. Conversely, destabilization of Sox2 by miR-21 can be blocked by anti-miR-21. Thus, the REST-miR-21-Sox2 axis connects REST to the core nuclear pluripotency regulators in E14Tg2a.4 mESCs cultured in the absence of feeder cells.
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Anantha
authors.initials: A
authors.lastname: Marisetty
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pratheesh
authors.initials: P
authors.lastname: Sathyan
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mohamedi
authors.initials: M
authors.lastname: Kagalwala
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: ssinghk@gmail.com.
authors.forename: Sadhan
authors.initials: S
authors.lastname: Majumder
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000099229:RE1-Silencing Transcription Factor
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C494174:Pou5f1 protein, mouse; C527783:Sox2 protein, mouse; C531950:MIRN21 microRNA, mouse
keywords: REST-miR-21-Sox2 axis in mESC pluripotency