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

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Item Type:	Article
Title:	Epigenomic profiling of human CD4(+) T cells supports a linear differentiation model and highlights molecular regulators of memory development
Creators Name:	Durek, P., Nordström, K., Gasparoni, G., Salhab, A., Kressler, C., de Almeida, M., Bassler, K., Ulas, T., Schmidt, F., Xiong, J., Glažar, P., Klironomos, F., Sinha, A., Kinkley, S., Yang, X., Arrigoni, L., Amirabad, A.., Ardakani, F.B., Feuerbach, L., Gorka, O., Ebert, P., Müller, F., Li, N., Frischbutter, S., Schlickeiser, S., Cendon, C., Fröhler, S., Felder, B., Gasparoni, N., Imbusch, C.D., Hutter, B., Zipprich, G., Tauchmann, Y., Reinke, S., Wassilew, G., Hoffmann, U., Richter, A.S., Sieverling, L., Chang, H.D., Syrbe, U., Kalus, U., Eils, J., Brors, B., Manke, T., Ruland, J., Lengauer, T., Rajewsky, N., Chen, W., Dong, J., Sawitzki, B., Chung, H.R., Rosenstiel, P., Schulz, M.H., Schultze, J.L., Radbruch, A., Walter, J., Hamann, A. and Polansky, J.K.
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.
Keywords:	CD4-Positive T-Lymphocytes, Cell Differentiation, Epigenomics, Flow Cytometry, Gene Expression Profiling, Genetic Epigenesis, Immunologic Memory, Machine Learning, Polymerase Chain Reaction, Transcriptome
Source:	Immunity
ISSN:	1074-7613
Publisher:	Cell Press
Volume:	45
Number:	5
Page Range:	1148-1161
Date:	15 November 2016
Official Publication:	https://doi.org/10.1016/j.immuni.2016.10.022
PubMed:	View item in PubMed

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