title: Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation.
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.
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;
authors: Ageliki
authors: A
authors: Tsagaratou
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;Department of Information and Computer Science, Aalto University School of Science, FI-00076 Aalto, Finland;
authors: Tarmo
authors: T
authors: Äijö
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;
authors: Chan-Wang J
authors: CW
authors: Lio
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;
authors: Xiaojing
authors: X
authors: Yue
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037;
authors: Yun
authors: Y
authors: Huang
authors: Howard Hughes Medical Institute,Department of Molecular, Cell, and Developmental Biology, andEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095; and.
authors: Steven E
authors: SE
authors: Jacobsen
authors: Department of Information and Computer Science, Aalto University School of Science, FI-00076 Aalto, Finland;
authors: Harri
authors: H
authors: Lähdesmäki
authors: Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92034;Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037;Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093 arao@liai.org.
authors: Anjana
authors: A
authors: Rao
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: epigenetics; thymic development