Histone architecture of stem-cell memory T cells reveals progressive remodeling of epigenetic landscape in antigen-experienced CD8 T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Nicholas Restifo
PROVIDER: E-GEOD-67881 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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 gene expression changes over time during human CD4+T-cell polarization towards Th1 and Th2. Gene expression was assessed in relationship to 5hmC and DNA methylation levels and changes (see data series), we observed characteristic gene expression for the specific time points and stimuli or cell type and the expression was correlated with gene body 5hmC as well as anticorrelated with promoter DNA methylation levels. This submission contains data from transcription profiling by array of human CD4+T-cells, Th1/Th2 polarized time-series and primary memory subsets. It is part of series containing 5hmC and DNA methylation profiling of the same samples. See related experiments E-MTAB-4685, E-MTAB-4686, E-MTAB-4688, E-MTAB-4689.
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