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Epigenomic profiling of human CD4+ T cells supports a linear differentiation model and highlights molecular regulators of memory development

Official URL:https://doi.org/10.1016/j.immuni.2016.10.022
PubMed:View item in PubMed
Creators Name:Durek, P. and Nordstroem, K. and Gasparoni, G. and Salhab, A. and Kressler, C. and de Almeida, M. and Bassler, K. and Ulas, T. and Schmidt, F. and Xiong, J. and Glazar, P. and Klironomos, F. and Sinha, A. and Kinkley, S. and Yang, X. and Arrigoni, L. and Amirabad, A.. and Ardakani, F.B. and Feuerbach, L. and Gorka, O. and Ebert, P. and Mueller, F. and Li, N. and Frischbutter, S. and Schlickeiser, S. and Cendon, C. and Froehler, S. and Felder, B. and Gasparoni, N. and Imbusch, C.D. and Hutter, B. and Zipprich, G. and Tauchmann, Y. and Reinke, S. and Wassilew, G. and Hoffmann, U. and Richter, A.S. and Sieverling, L. and Chang, H.D. and Syrbe, U. and Kalus, U. and Eils, J. and Brors, B. and Manke, T. and Ruland, J. and Lengauer, T. and Rajewsky, N. and Chen, W. and Dong, J. and Sawitzki, B. and Chung, H.R. and Rosenstiel, P. and Schulz, M.H. and Schultze, J.L. and Radbruch, A. and Walter, J. and Hamann, A. and Polansky, J.K.
Journal Title:Immunity
Journal Abbreviation:Immunity
Volume:45
Number:5
Page Range:1148-1161
Date:15 November 2016
Abstract:The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators.
ISSN:1074-7613
Publisher:Cell Press (U.S.A.)
Item Type:Article

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