title: Reprogramming of Polycomb-Mediated Gene Silencing in Embryonic Stem Cells by the miR-290 Family and the Methyltransferase Ash1l.
abstract: Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR(-/-) ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Polycomb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family.
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Chryssa
authors.initials: C
authors.lastname: Kanellopoulou
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Gilpatrick
authors.affiliation: Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Gokhul
authors.initials: G
authors.lastname: Kilaru
authors.affiliation: Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Burr
authors.affiliation: Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Cuong K
authors.initials: CK
authors.lastname: Nguyen
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Morawski
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Electronic address: mlenardo@niaid.nih.gov.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
authors.affiliation: Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Electronic address: stefan.muljo@nih.gov.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Muljo
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020868:Gene Silencing; D005801:Genes, Homeobox; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000611398:MIRN-291 microRNA, mouse; D035683:MicroRNAs; D063146:Polycomb-Group Proteins; C000600280:Ash1l protein, mouse; D011495:Histone-Lysine N-Methyltransferase