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http://purl.uniprot.org/citations/31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31171699http://www.w3.org/2000/01/rdf-schema#comment"Mouse embryonic stem cell (ESC) cultures contain a rare cell population of "2C-like" cells resembling two-cell embryos, the key stage of zygotic genome activation (ZGA). Little is known about positive regulators of the 2C-like state and two-cell stage embryos. Here we show that GADD45 (growth arrest and DNA damage 45) proteins, regulators of TET (TET methylcytosine dioxygenase)-mediated DNA demethylation, promote both states. Methylome analysis of Gadd45a,b,g triple-knockout (TKO) ESCs reveal locus-specific DNA hypermethylation of ∼7000 sites, which are enriched for enhancers and loci undergoing TET-TDG (thymine DNA glycosylase)-mediated demethylation. Gene expression is misregulated in TKOs, notably upon differentiation, and displays signatures of DNMT (DNA methyltransferase) and TET targets. TKOs manifest impaired transition into the 2C-like state and exhibit DNA hypermethylation and down-regulation of 2C-like state-specific genes. Gadd45a,b double-mutant mouse embryos display embryonic sublethality, deregulated ZGA gene expression, and developmental arrest. Our study reveals an unexpected role of GADD45 proteins in embryonic two-cell stage regulation."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.org/dc/terms/identifier"doi:10.1101/gad.325696.119"xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Karaulanov E."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Niehrs C."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Leichsenring M."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Musheev M.U."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Andreani T."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Mallick M."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Vastolo V."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/author"Schule K.M."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/name"Genes Dev"xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/pages"782-798"xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/title"GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells."xsd:string
http://purl.uniprot.org/citations/31171699http://purl.uniprot.org/core/volume"33"xsd:string
http://purl.uniprot.org/citations/31171699http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31171699
http://purl.uniprot.org/citations/31171699http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31171699
http://purl.uniprot.org/uniprot/#_A0A0N4SVJ9-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/#_A0A0N4SW99-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/#_A0A1W2P6W4-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/#_Q3UMH6-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/#_P22339-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/#_P48316-mappedCitation-31171699http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31171699
http://purl.uniprot.org/uniprot/P48316http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31171699