Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation

Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):E3306-15. doi: 10.1073/pnas.1412327111. Epub 2014 Jul 28.

Abstract

The discovery of Ten Eleven Translocation proteins, enzymes that oxidize 5-methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T-cell development in the thymus and T-cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T-cell development and differentiation.

Keywords: epigenetics; thymic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Lineage / genetics
  • Cell Lineage / physiology
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proto-Oncogene Proteins / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine

Associated data

  • GEO/GSE59213