| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print June 7, 2005
German Arthritis Research Centre Berlin, Berlin 10117
Corresponding Author: tykocinski{at}drfz.de
Naïve T helper (Th) lymphocytes are induced to express the interleukin-4 (il4) gene by simultaneous signaling through the T cell receptor (TcR) and the IL-4 receptor. Upon restimulation with antigen such preactivated Th lymphocytes can reexpress the il4 gene independent of IL-4 receptor signaling. This memory for expression of the il4 gene depends on epigenetic modification of the il4 gene locus and an increased expression of GATA-3, the key transcription factor for Th2 differentiation. Here, we have identified a phylogenetically conserved sequence (conserved intronic regulatory element, CIRE) in the first intron of the il4 gene containing a tandem GATA-3 binding site. We show that GATA-3 binds to this sequence in a position- and orientation-dependent manner, in vitro and in vivo. DNA demethylation and histone acetylation of this region occurs early and selectively in differentiating, IL-4-secreting Th2 lymphocytes. Deletion of the conserved element by replacement of the first exon and part of the first intron of the il4 gene with gfp leads to a defect in the establishment of memory for expression of IL-4, in that reexpression of IL-4 still requires costimulation by exogenous IL-4. The CIRE thus links the initial epigenetic modification of the il4 gene to GATA-3 and serves as a genetic control element for memory expression of IL-4.
J. Biol. Chem, 10.1074/jbc.M502038200
Submitted on February 23, 2005
Revised on May 18, 2005
Accepted on June 7, 2005
A critical control element for interleukin-4 memory expression in T helper lymphocytes
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. de Lalla, N. Festuccia, I. Albrecht, H.-D. Chang, G. Andolfi, U. Benninghoff, F. Bombelli, G. Borsellino, A. Aiuti, A. Radbruch, et al. Innate-Like Effector Differentiation of Human Invariant NKT Cells Driven by IL-7 J. Immunol., April 1, 2008; 180(7): 4415 - 4424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Miller and S.-m. Ho Environmental Epigenetics and Asthma: Current Concepts and Call for Studies Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 567 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, M. Ballaney, U. Al-alem, C. Quan, X. Jin, F. Perera, L.-C. Chen, and R. L. Miller Combined Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo Toxicol. Sci., March 1, 2008; 102(1): 76 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Kim, P. E. Fields, and R. A. Flavell Demethylation of a specific hypersensitive site in the Th2 locus control region PNAS, October 23, 2007; 104(43): 17052 - 17057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rose, M. Lichtenheld, M. R. Foote, and B. Adkins Murine Neonatal CD4+ Cells Are Poised for Rapid Th2 Effector-Like Function J. Immunol., March 1, 2007; 178(5): 2667 - 2678. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
