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TET1 is a maintenance DNA demethylase that prevents methylation spreading in adult cells [RNA-seq]

ABSTRACT: We report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells. Genome-wdie profiling of gene expression in HEK293T cells following overexpression of wild type or catalytically mutant TET1-FL or TET1-CD

ORGANISM(S): Homo sapiens

SUBMITTER: CHUNLEI JIN 

PROVIDER: E-GEOD-49833 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.

Jin Chunlei C   Lu Yue Y   Jelinek Jaroslav J   Liang Shoudan S   Estecio Marcos R H MR   Barton Michelle Craig MC   Issa Jean-Pierre J JP  

Nucleic acids research 20140529 11

TET1 is a 5-methylcytosine dioxygenase and its DNA demethylating activity has been implicated in pluripotency and reprogramming. However, the precise role of TET1 in DNA methylation regulation outside of developmental reprogramming is still unclear. Here, we show that overexpression of the TET1 catalytic domain but not full length TET1 (TET1-FL) induces massive global DNA demethylation in differentiated cells. Genome-wide mapping reveals that 5-hydroxymethylcytosine production by TET1-FL is inhi  ...[more]

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