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  Identification of Two Novel Regulatory Elements in the IL2RA Gene Locus

Rosa, F., Rameil, P., Algarté-Génin, M., Bedotto, M., Ferrier, P., Cauchy, P., et al. (2018). Identification of Two Novel Regulatory Elements in the IL2RA Gene Locus. Journal of Pulmonary & Respiratory Medicine, 8, 1000458. doi:10.4172/2161-105X.1000458.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-6E85-C Version Permalink: http://hdl.handle.net/21.11116/0000-0004-DBCB-1
Genre: Journal Article

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 Creators:
Rosa, F.1, Author
Rameil, P.1, Author
Algarté-Génin, M.1, Author
Bedotto, M.1, Author
Ferrier , P.1, Author
Cauchy, Pierre2, Author              
Imbert, J.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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Free keywords: IL2RA, Enhancer, Regulatory T-cell, Gene regulation, CREB, PARP-1, EMSA
 Abstract: Regulatory T-cells Tregs express the high-affinity chain of the interleukin 2 (IL-2) receptor, CD25, encoded by the IL2RA gene. IL2RA is one of the most extensively characterized genes regarding its regulatory regions and their functional links to cell surface receptors and their associated signal transduction cascade in the context of the antigen-dependent activation of mature CD4+ T lymphocyte. However, converging evidences strongly suggested that they were some missing pieces in this already complex puzzle made of 6 well-characterized regulatory regions. Here, by combining principally in silico genomic footprinting approach and meta-analysis of several ChIP-seq studies, we identified and characterized 2 new putative CD28-responsive elements. We show that a recently-characterized intronic enhancer at +11 kb harbors a functional CREB site. Further, we evidence a repressor element consisting of two GAAA repeats located 5’-most of a previously identified enhancer 4 kb upstream of the IL2RA gene. Massspectrometry analyses revealed Poly ADP-ribose polymerase 1 (PARP-1) as part of the complexes binding this element. Altogether, our observations extend our understanding of the molecular basis of the multiple options offered by such a complex organization in term of T cell responses.

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Language(s): eng - English
 Dates: 2018-05-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.4172/2161-105X.1000458
 Degree: -

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Title: Journal of Pulmonary & Respiratory Medicine
Source Genre: Journal
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Pages: - Volume / Issue: 8 Sequence Number: - Start / End Page: 1000458 Identifier: -