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http://purl.uniprot.org/citations/22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22210859http://www.w3.org/2000/01/rdf-schema#comment"The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic data sets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripotency in mESCs partly by opposing MAPK/ERK-mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1's normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkr1253"xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Ghosh S."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Hu G."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Li R."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Zheng X."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Wade P.A."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Freudenberg J.M."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Jothi R."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Lackford B.L."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Cuddapah S."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/author"Yellaboina S."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/name"Nucleic Acids Res"xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/pages"3364-3377"xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/title"Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity."xsd:string
http://purl.uniprot.org/citations/22210859http://purl.uniprot.org/core/volume"40"xsd:string
http://purl.uniprot.org/citations/22210859http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22210859
http://purl.uniprot.org/citations/22210859http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22210859
http://purl.uniprot.org/uniprot/#_A0A0B7MAW8-mappedCitation-22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22210859
http://purl.uniprot.org/uniprot/#_A0A0B7MHT7-mappedCitation-22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22210859
http://purl.uniprot.org/uniprot/#_A0A0B7MHU2-mappedCitation-22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22210859
http://purl.uniprot.org/uniprot/#_A0A0B7MGW8-mappedCitation-22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22210859
http://purl.uniprot.org/uniprot/#_A0A0B7MG67-mappedCitation-22210859http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22210859