ArticleCell reports2015
PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells.
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Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 76 citations in OpenAlex.
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- Role of MEG3-miRNAs in immune-inflammatory regulation in age-dependent wool follicle remodeling in Tan sheep.BMC genomics · 2026Article
- The superpowers of imprinting control regions.Genome research · 2026Review
- Differential epigenetic regulation of glucose-induced alteration of miR-9 in retinal and cardiac endothelial cells.PloS one · 2026Article
- 5-mC DNA methylation in neurodevelopment: from molecular mechanisms to therapeutic implications.Molecular biology reports · 2025Review
- DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Identification of maternal allele sequences of IG-DMR that are essential for neonatal viability.PloS one · 2025Article
- DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.Cell death & disease · 2024Article
- The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation.Nucleic acids research · 2024Article
- Protein restriction during pregnancy alters Cdkn1c silencing, dopamine circuitry and offspring behaviour without changing expression of key neuronal marker genes.Scientific reports · 2024Article
- Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature.Communications biology · 2024Article
- Transgenerational Epigenetic DNA Methylation Editing and Human Disease.Biomolecules · 2023Review
- Epigenetic mechanism of Gtl2-miRNAs causes the primitive sheep characteristics found in purebred Merino sheep.Cell & bioscience · 2023Article
- Imprinted Long Non-Coding RNAs in Mammalian Development and Disease.International journal of molecular sciences · 2023Review
- Dlk1-Dio3 cluster miRNAs regulate mitochondrial functions in the dystrophic muscle in Duchenne muscular dystrophy.Life science alliance · 2023Article
- Balanced gene dosage control rather than parental origin underpins genomic imprinting.Nature communications · 2022Article
- RBBP4 dysfunction reshapes the genomic landscape of H3K27 methylation and acetylation and disrupts gene expression.G3 (Bethesda, Md.) · 2022Article
- Epigenome editing reveals core DNA methylation for imprinting control in the Dlk1-Dio3 imprinted domain.Nucleic acids research · 2022Article
- Identification of the porcine IG-DMR and abnormal imprinting ofFrontiers in cell and developmental biology · 2022Article
- A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.Developmental cell · 2021Article
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Authors and funding
25 authors at 5 institutions in 1 country.
Partha Pratim DasDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute (HHMI), Boston, MA 02115, USA.
David A HendrixComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Department of Biochemistry and Biophysics, School of Electrical Engineering and Computer Science, Oregon State University, 2011 Ag and Life Science Building, Corvallis, OR 97331-7305, USA.
Effie ApostolouDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA.
Alice H BuchnerDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Molecular Biology Program, International Max Planck Research School, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
Matthew C CanverDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Semir BeyazDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Damir LjubojaDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Rachael KuintzleDepartment of Biochemistry and Biophysics, School of Electrical Engineering and Computer Science, Oregon State University, 2011 Ag and Life Science Building, Corvallis, OR 97331-7305, USA.
Woojin KimDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Rahul KarnikDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Zhen ShaoDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Huafeng XieDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Jian XuDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Alejandro De Los AngelesDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Yingying ZhangDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Junho ChoeStem Cell Program, Department of Biological Chemistry and Molecular Pharmacology and Department of Pediatrics, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Don Leong Jia JunDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; School of Chemical and Life Sciences, Singapore Polytechnic, 500 Dover Road, Singapore 139651, Singapore.
Xiaohua ShenDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Richard I GregoryStem Cell Program, Department of Biological Chemistry and Molecular Pharmacology and Department of Pediatrics, Boston Children's Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
George Q DaleyDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute (HHMI), Boston, MA 02115, USA.
Alexander MeissnerDepartment of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Manolis KellisComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Konrad HochedlingerHoward Hughes Medical Institute (HHMI), Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA.
Jonghwan KimDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Stuart H OrkinDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute (DFCI), Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute (HHMI), Boston, MA 02115, USA. Electronic address: stuart_orkin@dfci.harvard.edu.
Harvard University · USBoston Children's Hospital · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · USOregon State University · US
Funding
Human Pluripotent Stem Cell and Progenitor Models of Cardiac and Blood DiseasesU01HL100001 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, ORKIN, STUART H · 2009 to 2015
$8.9MMechanistic roles of BCL11A in globin switching and fetal hemoglobin silencingK01DK093543 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI XU, JIAN · 2011 to 2015
$732kIdentification of Novel Regulators of Fetal Hemoglobin ExpressionF30DK103359 · NIDDK · HARVARD MEDICAL SCHOOL · PI CANVER, MATTHEW CHARLES · 2015 to 2017
$131kHoward Hughes Medical InstituteNHLBI NIH HHS U01 HL100001NHLBI NIH HHS U01HL100001NIDDK NIH HHS F30 DK103359NIDDK NIH HHS F30 DK103359-01A1NIDDK NIH HHS K01 DK093543
Abstract
Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency.
Indexed as
DNA MethylationGenomic ImprintingAnimalsCell LineDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEmbryonic Stem CellsMiceMicroRNAsNuclear ProteinsPolycomb Repressive Complex 2Protein BindingRNA, Long NoncodingDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AMEG3 non-coding RNA, mouseMicroRNAsNuclear ProteinsPolycomb Repressive Complex 2Rian protein, mouseRNA, Long Noncoding
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