Epigenomic Profiling of Human CD4<sup>+</sup> T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development
- 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.
- Feuerbach, L.
- Gorka, O.
- Ebert, P.
- Müller, F.
- Li, N.
- Frischbutter, S.
- Schlickeiser, S.
- Cendon, C.
- Fröhler, S.
- Felder, B.
- Gasparoni, N.
- Imbusch, C.
- Hutter, B.
- Zipprich, G.
- Tauchmann, Y.
- Reinke, S.
- Wassilew, G.
- Hoffmann, U.
- Richter, A.
- Sieverling, L.
- Consortium, D.
- Chang, H.
- Syrbe, U.
- Kalus, U.
- Eils, J.
- Brors, B.
- Manke, T.
- Ruland, J.
- Lengauer, T.
- Rajewsky, N.
- Chen, W.
- Dong, J.
- Sawitzki, B.
- Chung, H.
- Rosenstiel, P.
- Schulz, M.
- Schultze, J.
- Radbruch, A.
- Walter, J.
- Hamann, A.
- Polansky, J.
DOIAbstract
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-Tm...
Add to ORKG