The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations

Schmidl, Christian, Hansmann, Leo, Lassmann, Timo, Balwierz, Piotr J., Kawaji, Hideya, Itoh, Masayoshi, Kawai, Jun, Nagao-Sato, Sayaka, Suzuki, Harukazu, Andreesen, Reinhard, Hayashizaki, Yoshihide, Forrest, Alistair R. R., Carninci, Piero, Hoffmann, Petra, Edinger, Matthias, Rehli, Michael, for the FANTOM consortium, Wells, Christine and Wolvetang, Ernst (2014) The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations. Blood, 123 17: e68-e78. doi:10.1182/blood-2013-02-486944

Author Schmidl, Christian
Hansmann, Leo
Lassmann, Timo
Balwierz, Piotr J.
Kawaji, Hideya
Itoh, Masayoshi
Kawai, Jun
Nagao-Sato, Sayaka
Suzuki, Harukazu
Andreesen, Reinhard
Hayashizaki, Yoshihide
Forrest, Alistair R. R.
Carninci, Piero
Hoffmann, Petra
Edinger, Matthias
Rehli, Michael
for the FANTOM consortium
Wells, Christine
Wolvetang, Ernst
Title The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2014-04-24
Sub-type Article (original research)
DOI 10.1182/blood-2013-02-486944
Open Access Status DOI
Volume 123
Issue 17
Start page e68
End page e78
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
Key Points
• Transcription and enhancer profiling reveal cell type–specific regulome architectures and transcription factor networks in conventional and regulatory T cells.

CD4+CD25+FOXP3+ human regulatory T cells (Tregs) are essential for self-tolerance and immune homeostasis. Here, we describe the promoterome of CD4+CD25highCD45RA+ naïve and CD4+CD25highCD45RA 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published FANTOM authors are "for the FANTOM consortium".

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 27 Jun 2014, 00:34:31 EST by Cathy Fouhy on behalf of Institute for Molecular Bioscience