Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation 
Model and Highlights Molecular Regulators of Memory Development

Durek, Pawel; Nordström, Karl; Gasparoni, Gilles; Salhab, Abdulrahman; Kressler, Christopher; de Almeida, Melanie; Bassler, Kevin; Ulas, Thomas; Schmidt, Florian; Xiong, Jieyi; Glažar, Petar; Klironomos, Filippos; Sinha, Anupam; Kinkley, Sarah; Yang, Xinyi; Arrigoni, Laura; Amirabad, Azim Dehghani; Ardakani, Fatemeh Behjati; Feuerbach, Lars; Gorka, Oliver; Ebert, Peter; Müller, Fabian; Li, Na; Frischbutter, Stefan; Schlickeiser, Stephan; Cendon, Carla; Fröhler, Sebastian; Felder, Bärbel; Gasparoni, Nina; Imbusch, Charles D.; Hutter, Barbara; Zipprich, Gideon; Tauchmann, Yvonne; Reinke, Simon; Wassilew, Georgi; Hoffmann, Ute; Richter, Andreas S.; Sieverling, Lina; Consortium, DEEP; Chang, Hyun-Dong; Syrbe, Uta; Kalus, Ulrich; Eils, Jürgen; Brors, Benedikt; Manke, Thomas; Ruland, Jürgen; Lengauer, Thomas; Rajewsky, Nikolaus; Chen, Wei; Dong, Jun; Sawitzki, Birgit; Chung, Ho-Ryun; Rosenstiel, Philip; Schulz, Marcel H.; Schultze, Joachim L.; Radbruch, Andreas; Walter, Jörn; Hamann, Alf; Polansky, Julia K.

doi:10.1016/j.immuni.2016.10.022

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Epigenomic Profiling of Human CD4⁺ 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., et al. (2016). Epigenomic Profiling of Human CD4⁺ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development. Immunity, 45, 1148-1161. doi:10.1016/j.immuni.2016.10.022.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-AF37-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-9B03-6

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https://www.sciencedirect.com/science/article/pii/S1074761316304332?via%3Dihub (Publisher version) Open Access status unknown

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Durek, Pawel¹, Author
Nordström, Karl¹, Author
Gasparoni, Gilles¹, Author
Salhab, Abdulrahman¹, Author
Kressler, Christopher¹, Author
de Almeida, Melanie¹, Author
Bassler, Kevin¹, Author
Ulas, Thomas¹, Author
Schmidt, Florian¹, Author
Xiong, Jieyi¹, Author
Glažar, Petar¹, Author
Klironomos, Filippos¹, Author
Sinha, Anupam¹, Author
Kinkley, Sarah¹, Author
Yang, Xinyi¹, Author
Arrigoni, Laura¹, Author
Amirabad, Azim Dehghani¹, Author
Ardakani, Fatemeh Behjati¹, Author
Feuerbach, Lars¹, Author
Gorka, Oliver¹, Author
Ebert, Peter¹, AuthorMüller, Fabian¹, AuthorLi, Na¹, AuthorFrischbutter, Stefan¹, AuthorSchlickeiser, Stephan¹, AuthorCendon, Carla¹, AuthorFröhler, Sebastian¹, AuthorFelder, Bärbel¹, AuthorGasparoni, Nina¹, AuthorImbusch, Charles D.¹, AuthorHutter, Barbara¹, AuthorZipprich, Gideon¹, AuthorTauchmann, Yvonne¹, AuthorReinke, Simon¹, AuthorWassilew, Georgi¹, AuthorHoffmann, Ute¹, AuthorRichter, Andreas S.¹, AuthorSieverling, Lina¹, AuthorConsortium, DEEP¹, AuthorChang, Hyun-Dong¹, AuthorSyrbe, Uta¹, AuthorKalus, Ulrich¹, AuthorEils, Jürgen¹, AuthorBrors, Benedikt¹, AuthorManke, Thomas², AuthorRuland, Jürgen¹, AuthorLengauer, Thomas¹, AuthorRajewsky, Nikolaus¹, AuthorChen, Wei¹, AuthorDong, Jun¹, AuthorSawitzki, Birgit¹, AuthorChung, Ho-Ryun¹, AuthorRosenstiel, Philip¹, AuthorSchulz, Marcel H.¹, AuthorSchultze, Joachim L.¹, AuthorRadbruch, Andreas¹, AuthorWalter, Jörn¹, AuthorHamann, Alf¹, AuthorPolansky, Julia K.¹, Author more..

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1External Organizations, ou_persistent22
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640

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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.

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Language(s): eng - English

Dates: Date issued: 2016-11-15

Publication Status: Issued

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Rev. Type: Peer

Identifiers: DOI: 10.1016/j.immuni.2016.10.022

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Title: Immunity

Source Genre: Journal

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Publ. Info: Cambridge, Mass. : Cell Press

Pages: - Volume / Issue: 45 Sequence Number: - Start / End Page: 1148 - 1161 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783