Genomics

Dataset Information

295

A Primary Role of TET Proteins in Establishment and Maintenance of De Novo Bivalency at CpG Islands of Developmental Genes


ABSTRACT: TET protein-catalyzed 5mC oxidation not only creates novel DNA modifications such as 5hmC, but also initiates active or passive DNA demethylation. However, the TETs’ function in crosstalk with specific histone modifications is largely elusive. Here, we show that TET2-mediated DNA demethylation plays a primary role in the de novo establishment and maintenance of H3K4me3/H3K27me3 bivalent domain underlying the methylated DNA CpG islands (CGIs). Overexpression of wild type (WT) but not catalytic inactive mutant (Mut) TET2 in TET-low-expressing cells results in increase of 5hmC level and accompanying DNA demethylation at a subset of CGIs. Importantly, this is sufficient to create de novo bivalent domains at these loci. Genome-wide analysis reveals that these de novo synthesized bivalent domains are largely associated with a subset of key developmental gene promoters, which are often located within CpG islands that are previously hyper-methylated and silenced. On the other hand, depletion of Tet1 and Tet2 in mouse ES cells results in an apparent loss of H3K27me3 at bivalent domains, which are located within CGIs and associated with a particular set of key developmental gene promoters. Collectively, these data suggest that TET proteins have a primary role in charge of regulating the crosstalk between two key epigenetic mechanisms, DNA methylation and histone methylation (H3K4me3 and H3K27me3), particularly at a subset of CpG islands associated with developmental genes. We examined H3K4me3,H3K27me3,5mC and 5hmC in 293T and mES cell types,using Illumina Hiseq2500.

ORGANISM(S): Musculus  

SUBMITTER: Lingchun Kong   Ruitu Lv  Shi Yang 

PROVIDER: E-GEOD-72481 | ArrayExpress | 2016-07-25

SECONDARY ACCESSION(S): SRP062940GSE72481PRJNA294136

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands.

Kong Lingchun L   Tan Li L   Lv Ruitu R   Shi Zhennan Z   Xiong Lijun L   Wu Feizhen F   Rabidou Kimberlie K   Smith Michael M   He Celestine C   Zhang Lei L   Qian Yanyan Y   Ma Duan D   Lan Fei F   Shi Yang Y   Shi Yujiang Geno YG  

Nucleic acids research 20160610 18


Ten Eleven Translocation (TET) protein-catalyzed 5mC oxidation not only creates novel DNA modifications, such as 5hmC, but also initiates active or passive DNA demethylation. TETs' role in the crosstalk with specific histone modifications, however, is largely elusive. Here, we show that TET2-mediated DNA demethylation plays a primary role in the de novo establishment and maintenance of H3K4me3/H3K27me3 bivalent domains underlying methylated DNA CpG islands (CGIs). Overexpression of wild type (WT  ...[more]

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