Title |
The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations
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Published in |
Blood, March 2014
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DOI | 10.1182/blood-2013-02-486944 |
Pubmed ID | |
Authors |
Christian Schmidl, Leo Hansmann, Timo Lassmann, Piotr J. Balwierz, Hideya Kawaji, Masayoshi Itoh, Jun Kawai, Sayaka Nagao-Sato, Harukazu Suzuki, Reinhard Andreesen, Yoshihide Hayashizaki, Alistair R.R. Forrest, Piero Carninci, Petra Hoffmann, Matthias Edinger, Michael Rehli, for the FANTOM consortium |
Abstract |
CD4(+)CD25(+)FOXP3(+) human regulatory T cells (Tregs) are essential for self-tolerance and immune homeostasis. Here, we describe the promoterome of CD4(+)CD25(high)CD45RA(+) naïve and CD4(+)CD25(high)CD45RA(-) memory Tregs and their CD25(-) conventional T-cell (Tconv) counterparts both before and after in vitro expansion by cap analysis of gene expression (CAGE) adapted to single-molecule sequencing (HeliScopeCAGE). We performed comprehensive comparative digital gene expression analyses and revealed novel transcription start sites, of which several were validated as alternative promoters of known genes. For all in vitro expanded subsets, we additionally generated global maps of poised and active enhancer elements marked by histone H3 lysine 4 monomethylation and histone H3 lysine 27 acetylation, describe their cell type-specific motif signatures, and evaluate the role of candidate transcription factors STAT5, FOXP3, RUNX1, and ETS1 in both Treg- and Tconv-specific enhancer architectures. Network analyses of gene expression data revealed additional candidate transcription factors contributing to cell type specificity and a transcription factor network in Tregs that is dominated by FOXP3 interaction partners and targets. In summary, we provide a comprehensive and easily accessible resource of gene expression and gene regulation in human Treg and Tconv subpopulations. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 1 | <1% |
United States | 1 | <1% |
France | 1 | <1% |
Italy | 1 | <1% |
Unknown | 161 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 50 | 30% |
Student > Ph. D. Student | 39 | 24% |
Student > Master | 13 | 8% |
Other | 10 | 6% |
Student > Bachelor | 9 | 5% |
Other | 24 | 15% |
Unknown | 20 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 53 | 32% |
Biochemistry, Genetics and Molecular Biology | 33 | 20% |
Immunology and Microbiology | 27 | 16% |
Medicine and Dentistry | 16 | 10% |
Computer Science | 4 | 2% |
Other | 8 | 5% |
Unknown | 24 | 15% |