Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Christian Grosser

PROVIDER: E-GEOD-67351 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.

Grosser Christian C Wagner Nicholas N Grothaus Katrin K Horsthemke Bernhard B

Epigenetics 20150717 9

The TET family of dioxygenases (TET1/2/3) can convert 5-methylcytosine (5 mC) into 5-hydroxymethylcytosine (5 hmC) and has been shown to be involved in active and passive DNA demethylation. Here, we demonstrate that altering TET dioxygenase levels within physiological range can affect DNA methylation dynamics of HEK293 cells. Overexpression of TET1 increased global 5 hmC levels and was accompanied by mild DNA demethylation of promoters, gene bodies and CpG islands. Conversely, the simultaneous k ...[more]

PMID: 26186463

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Project description:Differentiation of CD4+T-cells into effector subsets is a critical component of the adaptive immune system and an incorrect response can lead to autoimmunity or immune deficiency. Cellular differentiation including T-cell differentiation is accompanied by large-scale epigenetic remodeling, including changes in DNA methylation at key regulators of T-cell differentiation. The TET family of enzymes were recently shown to be able to catalyse methylated cytosine (5mC) into 5-hydroxymethylcytosine (5hmC) enabling a pathway of active removal of DNA methylation. Here, we characterize 5hmC, 5mC and transcriptional dynamics during human CD4+T-cell polarisation in a time series approach and relate these changes to profiles in ex-vivo CD4+memory subsets. We observed large-scale remodelling during early CD4+T-cell differentiation which was predictive of subsequent changes during late time points, these changes were also related to disease associated regions which we show can act as functional regulatory elements. This dataset was designed to assess how TET1 affects gene expression during human CD4+T-cell differentiation. We observed that TET1 was highly expressed in primary lymphocytes compared to other human tissues and loss of TET1 gene expression was seen within 6 hours of naÃ¯ve CD4+T-cell activation. Primary human naÃ¯ve T-cells were transfected with different TET1 containing plasmids and polarized towards Th1 for 24h. When comparing cells transfected with full length TET1 to catalytically inactive TET1, we observed mis-expression of several cytokine/chemokine genes related to T-cell differentiation. This was not observed for cells expressing the catalytic domain of TET1. Note that the expression array only targets the DNA binding domain of the TET1 gene, therefore we validated ectopic expression of TET1 by qPCR targeting the catalytic domain. This submission contains data from Transcription profiling by array of primary human CD4+T-cells overexpressing TET1 polarized towards Th1. See related experiments: E-MTAB-4686, E-MTAB-4687, E-MTAB-4688, E-MTAB-4689.

Dataset Information

Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells

Publications

Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.

Similar Datasets

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