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Tet1 and Tet2 protect DNA methylation canyons against hypermethylation

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 intermedia...

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Bibliographic Details
Main Authors: Wiehle, Laura (Author) , Lyko, Frank (Author) , Breiling, Achim (Author)
Format: Article (Journal)
Language:English
Published: January 19, 2016
In: Molecular and cellular biology
Year: 2016, Volume: 36, Issue: 3, Pages: 452-461
ISSN:1098-5549
DOI:10.1128/MCB.00587-15
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1128/MCB.00587-15
Verlag, lizenzpflichtig, Volltext: https://mcb.asm.org/content/36/3/452
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Author Notes:Laura Wiehle, Günter Raddatz, Tanja Musch, Meelad M. Dawlaty, Rudolf Jaenisch, Frank Lyko, Achim Breiling
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Summary: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.
Item Description:Gesehen am 19.08.2020
Physical Description:Online Resource
ISSN:1098-5549
DOI:10.1128/MCB.00587-15

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