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ISSN: 2161-105X

Journal of Pulmonary & Respiratory Medicine
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  • Research Article   
  • J Pulm Respir Med 2018, Vol 8(2): 458
  • DOI: 10.4172/2161-105X.1000458

Identification of Two Novel Regulatory Elements in the IL2RA Gene Locus

Rosa F1,2, Rameil P3,4, Algarté-Génin M5, Bedotto M1,2, Ferrier P6,7, Cauchy P1,2,6,7,8* and Imbert J1,2*
1University of the Mediterranean, Marseille, France
2INSERM- National Institute of Health and Medical Research, , U1090, TAGC, Marseille, France
3INSERM- National Institute of Health and Medical Research, , UMR1068, CRCM, Marseille, France
4CNRS- National Center for Scientific Research, , UMR7258, CRCM, Marseille, France
5INSERM- National Institute of Health and Medical Research, , U943, Paris, France
6CNRS- National Centre for Scientific Research, , UMR7280, CIML, Marseille, France
7INSERM- National Institute of Health and Medical Research, , U1104, CIML, Marseille, France
8Max Planck Institute for Immunobiology and Epigenetics, , Freiburg, Germany
*Corresponding Author (s) : Cauchy P, Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany, Tel: (+49) (0)7615108730, Fax: (+49)(0)7615108220, Email: [email protected]
Imbert J, INSERM- National Institute of Health and Medical Research, U1090, TAGC, Marseille, France, Tel: (+33)(0)491828703, Fax: (+33)(0)491828700, Email: [email protected]

Received Date: Apr 30, 2018 / Accepted Date: May 03, 2018 / Published Date: May 09, 2018

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.

Keywords: IL2RA; Enhancer; Regulatory T-cell; Gene regulation; CREB; PARP-1; EMSA

Citation: Rosa F, Rameil P, Algarte-Genin M, Bedotto M, Ferrier P, et al. (2018) Identification of Two Novel Regulatory Elements in the IL2RA Gene Locus. J Pulm Respir Med 8: 458. Doi: 10.4172/2161-105X.1000458

Copyright: © 2018 Rosa F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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