Tet1 and Tet2 protect DNA methylation canyons against hypermethylation

• Verfasst von: Wiehle, Laura [VerfasserIn]
• Verfasst von: Lyko, Frank [VerfasserIn]
• Verfasst von: Breiling, Achim [VerfasserIn]
• Titel: Tet1 and Tet2 protect DNA methylation canyons against hypermethylation
• Verf.angabe: Laura Wiehle, Günter Raddatz, Tanja Musch, Meelad M. Dawlaty, Rudolf Jaenisch, Frank Lyko, Achim Breiling
• E-Jahr: 2016
• Jahr: January 19, 2016
• Umfang: 10 S.
• Fussnoten: Gesehen am 19.08.2020
• Titel Quelle: Enthalten in: Molecular and cellular biology
• Ort Quelle: London : Taylor & Francis, 1981
• Jahr Quelle: 2016
• Band/Heft Quelle: 36(2016), 3, Seite 452-461
• ISSN Quelle: 1098-5549
• DOI: doi:10.1128/MCB.00587-15
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1726746607

Abstract

DNA methylation is a dynamic epigenetic modification with an important role in cell fate specification and reprogramming. The Ten eleven translocation (Tet) family of enzymes converts 5-methylcytosine to 5-hydroxymethylcytosine, which promotes passive DNA demethylation and functions as an intermediate in an active DNA demethylation process. Tet1/Tet2 double-knockout mice are characterized by developmental defects and epigenetic instability, suggesting a requirement for Tet-mediated DNA demethylation for the proper regulation of gene expression during differentiation. Here, we used whole-genome bisulfite and transcriptome sequencing to characterize the underlying mechanisms. Our results uncover the hypermethylation of DNA methylation canyons as the genomic key feature of Tet1/Tet2 double-knockout mouse embryonic fibroblasts. Canyon hypermethylation coincided with disturbed regulation of associated genes, suggesting a mechanistic explanation for the observed Tet-dependent differentiation defects. Based on these results, we propose an important regulatory role of Tet-dependent DNA demethylation for the maintenance of DNA methylation canyons, which prevents invasive DNA methylation and allows functional regulation of canyon-associated genes.