Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide 5-hydroxymethylcytosine (5hmC) profiling by hMeDIP-seq in primary human CD4+T-cells polarized towards Th1 and Th2 time-series

ABSTRACT: 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 5-hydroxymethylcytosine (5hmC) changes over time during human CD4+T-cell polarization towards Th1 and Th2. We tested an early (1 day) and late (5 day) timepoint to distinguish between replication-independent (early) and replication-dependent (late) changes. When comparing the time-series profiles, we observed an early gain followed by a late loss of 5hmC suggesting active 5hmC remodelling precedes lineage specification in CD4+T-cells. This submission contains the data from genome-wide 5-hydroxymethylcytosine (5hmC) profiling by hMeDIP-seq in primary human CD4+T-cells polarized towards Th1 and Th2 time-series. This submission is part of series containing 5hmC and DNA methylation profiling of the same samples. See related experiments E-MTAB-4685, E-MTAB-4687, E-MTAB-4688, E-MTAB-4689.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Antonio Lentini

PROVIDER: E-MTAB-4686 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells.

Nestor Colm E CE Lentini Antonio A Hägg Nilsson Cathrine C Gawel Danuta R DR Gustafsson Mika M Mattson Lina L Wang Hui H Rundquist Olof O Meehan Richard R RR Klocke Bernward B Seifert Martin M Hauck Stefanie M SM Laumen Helmut H Zhang Huan H Benson Mikael M

Cell reports 20160623 2

5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function. We observe simi ...[more]

PMID: 27346350

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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

Genome-wide 5-hydroxymethylcytosine (5hmC) profiling by hMeDIP-seq in primary human CD4+T-cells polarized towards Th1 and Th2 time-series

Publications

5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells.

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