MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells

2008 ◽  
Vol 15 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Lasse Sinkkonen ◽  
Tabea Hugenschmidt ◽  
Philipp Berninger ◽  
Dimos Gaidatzis ◽  
Fabio Mohn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Transcriptional Repressors

scholarly journals DNMT1 regulates the timing of DNA methylation by DNMT3 in an enzymatic activity-dependent manner in mouse embryonic stem cells

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262277
Author(s):  
Takamasa Ito ◽  
Musashi Kubiura-Ichimaru ◽  
Yuri Murakami ◽  
Aaron B. Bogutz ◽  
Louis Lefebvre ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Enzymatic Activity ◽  
De Novo ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
S Phase ◽  
Dependent Manner ◽  
Activity Dependent

DNA methylation (DNAme; 5-methylcytosine, 5mC) plays an essential role in mammalian development, and the 5mC profile is regulated by a balance of opposing enzymatic activities: DNA methyltransferases (DNMTs) and Ten-eleven translocation dioxygenases (TETs). In mouse embryonic stem cells (ESCs), de novo DNAme by DNMT3 family enzymes, demethylation by the TET-mediated conversion of 5mC to 5-hydroxymethylation (5hmC), and maintenance of the remaining DNAme by DNMT1 are actively repeated throughout cell cycles, dynamically forming a constant 5mC profile. Nevertheless, the detailed mechanism and physiological significance of this active cyclic DNA modification in mouse ESCs remain unclear. Here by visualizing the localization of DNA modifications on metaphase chromosomes and comparing whole-genome methylation profiles before and after the mid-S phase in ESCs lacking Dnmt1 (1KO ESCs), we demonstrated that in 1KO ESCs, DNMT3-mediated remethylation was interrupted during and after DNA replication. This results in a marked asymmetry in the distribution of 5hmC between sister chromatids at mitosis, with one chromatid being almost no 5hmC. When introduced in 1KO ESCs, the catalytically inactive form of DNMT1 (DNMT1CI) induced an increase in DNAme in pericentric heterochromatin and the DNAme-independent repression of IAPEz, a retrotransposon family, in 1KO ESCs. However, DNMT1CI could not restore the ability of DNMT3 to methylate unmodified dsDNA de novo in S phase in 1KO ESCs. Furthermore, during in vitro differentiation into epiblasts, 1KO ESCs expressing DNMT1CI showed an even stronger tendency to differentiate into the primitive endoderm than 1KO ESCs and were readily reprogrammed into the primitive streak via an epiblast-like cell state, reconfirming the importance of DNMT1 enzymatic activity at the onset of epiblast differentiation. These results indicate a novel function of DNMT1, in which DNMT1 actively regulates the timing and genomic targets of de novo methylation by DNMT3 in an enzymatic activity-dependent and independent manner, respectively.

scholarly journals PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells

Cell Reports ◽  
2015 ◽  
Vol 12 (9) ◽  
pp. 1456-1470 ◽  
Author(s):  
Partha Pratim Das ◽  
David A. Hendrix ◽  
Effie Apostolou ◽  
Alice H. Buchner ◽  
Matthew C. Canver ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

scholarly journals Targeting of De Novo DNA Methylation Throughout the Oct-4 Gene Regulatory Region in Differentiating Embryonic Stem Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e9937 ◽  
Author(s):  
Rodoniki Athanasiadou ◽  
Dina de Sousa ◽  
Kevin Myant ◽  
Cara Merusi ◽  
Irina Stancheva ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
De Novo ◽  
Regulatory Region ◽  
Embryonic Stem ◽  
Gene Regulatory

DNA methylation in mouse embryonic stem cells and development

2007 ◽  
Vol 331 (1) ◽  
pp. 31-55 ◽  
Author(s):  
Tom Latham ◽  
Nick Gilbert ◽  
Bernard Ramsahoye
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

scholarly journals Identification of Novel miRNAs in Mouse Embryonic Stem Cells, Embryonic Fibroblasts, and Reprogrammed Pluripotent Cells

2019 ◽  
Author(s):  
Botao Zhao ◽  
Chunsun Fan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Mouse Embryonic Stem Cells ◽  
Pluripotent Cells ◽  
Embryonic Fibroblasts ◽  
Species Specific

AbstractMicroRNAs (miRNAs) are a class of non-coding small RNAs that function in almost every known cellular activity. MiRNAs play an important role in gene regulation that controls embryonic stem cell (ESC) pluripotency and differentiation, as well as induced pluripotent stem cell (iPSC) reprogramming. In this study, we identified nine novel miRNAs by mining the deep sequencing dataset from mouse embryonic stem cells, mouse embryonic fibroblasts (MEF) and three kinds of reprogrammed pluripotent cells. Most of them are non-conserved but species-specific and cell-specific miRNAs. Eight miRNAs are derived from gene introns, including a “mirtron” miRNA, miR-novel-41. We also showed that miR-novel-27 is a mouse-specific miRNA and the 5′ arm of its precursor hairpin, embedding the mature miR-novel-27, uniquely exists in mouse species but not in any other Placentalia animals. Notably, the 5′ arm of the pre-miR-novel-27 hairpin shows nearly perfect palindrome to the 3′ arm suggesting that it was generated by inverted duplication of the 3′ arm. By this mechanism, the pre-miR-novel-27 hairpin was de novo gained in the mouse genome. This is a new type of de novo miRNA emergence mechanism in animals, which we called “inverted local half hairpin duplication” here. In addition, very limited nucleotide mutants accumulated on the newly emerged 5′ arm since its birth suggesting an especially young evolutionary history of the miR-novel-27 gene.

scholarly journals Preferable in vitro condition for maintaining faithful DNA methylation imprinting in mouse embryonic stem cells

2018 ◽  
Vol 23 (3) ◽  
pp. 146-160 ◽  
Author(s):  
Jiyoung Lee ◽  
Ayumi Matsuzawa ◽  
Hirosuke Shiura ◽  
Akito Sutani ◽  
Fumitoshi Ishino
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

scholarly journals Zscan4 Inhibits Maintenance DNA Methylation to Facilitate Telomere Elongation in Mouse Embryonic Stem Cells

Cell Reports ◽  
2017 ◽  
Vol 20 (8) ◽  
pp. 1936-1949 ◽  
Author(s):  
Jiameng Dan ◽  
Philippe Rousseau ◽  
Swanand Hardikar ◽  
Nicolas Veland ◽  
Jiemin Wong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Telomere Elongation

scholarly journals Coordinate Regulation of DNA Methylation and H3K27me3 in Mouse Embryonic Stem Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53880 ◽  
Author(s):  
James A. Hagarman ◽  
Michael P. Motley ◽  
Katla Kristjansdottir ◽  
Paul D. Soloway
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Coordinate Regulation

scholarly journals Normal DNA Methylation Dynamics in DICER1-Deficient Mouse Embryonic Stem Cells

PLoS Genetics ◽  
2012 ◽  
Vol 8 (9) ◽  
pp. e1002919 ◽  
Author(s):  
Jonathan Ip ◽  
Paul Canham ◽  
K. H. Andy Choo ◽  
Yoshimi Inaba ◽  
Shelley A. Jacobs ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Deficient Mouse
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