| Literature DB >> 27851915 |
Pawel Durek1, Karl Nordström2, Gilles Gasparoni2, Abdulrahman Salhab2, Christopher Kressler1, Melanie de Almeida1, Kevin Bassler3, Thomas Ulas3, Florian Schmidt4, Jieyi Xiong5, Petar Glažar6, Filippos Klironomos6, Anupam Sinha7, Sarah Kinkley8, Xinyi Yang8, Laura Arrigoni9, Azim Dehghani Amirabad4, Fatemeh Behjati Ardakani4, Lars Feuerbach10, Oliver Gorka11, Peter Ebert12, Fabian Müller12, Na Li8, Stefan Frischbutter1, Stephan Schlickeiser13, Carla Cendon14, Sebastian Fröhler5, Bärbel Felder15, Nina Gasparoni2, Charles D Imbusch10, Barbara Hutter10, Gideon Zipprich15, Yvonne Tauchmann16, Simon Reinke17, Georgi Wassilew18, Ute Hoffmann1, Andreas S Richter9, Lina Sieverling10, Hyun-Dong Chang14, Uta Syrbe19, Ulrich Kalus16, Jürgen Eils15, Benedikt Brors10, Thomas Manke9, Jürgen Ruland20, Thomas Lengauer12, Nikolaus Rajewsky6, Wei Chen5, Jun Dong14, Birgit Sawitzki13, Ho-Ryun Chung8, Philip Rosenstiel7, Marcel H Schulz4, Joachim L Schultze3, Andreas Radbruch14, Jörn Walter2, Alf Hamann1, Julia K Polansky21.
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.Entities:
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Year: 2016 PMID： 27851915 DOI： 10.1016/j.immuni.2016.10.022
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745