Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity

• Published in: Nucleic acids research Vol. 40; no. 8; pp. 3364 - 3377
• Main Authors: Freudenberg, Johannes M, Ghosh, Swati, Lackford, Brad L, Yellaboina, Sailu, Zheng, Xiaofeng, Li, Ruifang, Cuddapah, Suresh, Wade, Paul A, Hu, Guang, Jothi, Raja
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2012
• Subjects: 5-Methylcytosine - analogs & derivatives; Animals; Cells, Cultured; Chromatin; Cytosine - analogs & derivatives; Cytosine - metabolism; Data processing; Demethylation; Differentiation; DNA; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methyltransferase 3B; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Embryo cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - enzymology; Embryonic Stem Cells - metabolism; Enzymes; Extracellular signal-regulated kinase; Gene Expression Profiling; Gene Expression Regulation; Gene Regulation, Chromatin and Epigenetics; genomics; Homeodomain Proteins - metabolism; Leukemia inhibitory factor; Leukemia Inhibitory Factor - metabolism; MAP kinase; MAP Kinase Signaling System; Mice; Nanog Homeobox Protein; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Reviews; RNA Interference; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - metabolism; Stem cells; Transcription activation

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 (mESC...