Coordinated regulation of IL-4 and IL-13 expression in human T cells: 3C analysis for DNA looping

Biochem Biophys Res Commun. 2012 Jan 20;417(3):996-1001. doi: 10.1016/j.bbrc.2011.12.069. Epub 2011 Dec 27.

Abstract

Asthma is a chronic allergic disorder characterised by chronic inflammation. The balance of type I and type II (CD4+) T helper cells is of critical importance. In asthma there is an overexpression of T(H)2 cytokines, such as IL-4, IL-5 and IL-13. The genes encoding these cytokines are located together the same chromosomal region, 5q31.1 in humans. Here we confirm a central role for the transcription factors NFAT and GATA3 in the regulation of human IL-4 and IL-13. Chromatin Conformation Capture (3C) demonstrated the formation of specific ligation products containing spliced IL-4 and IL-13 DNA sequences in human T(H)2 polarised HuT-78 cells. This suggests that co-ordinate expression of T(H)2 cytokines, under the control of GATA3 and NFAT1 is due to the formation of a chromatin hub by DNA looping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / immunology*
  • Base Sequence
  • CD28 Antigens / immunology
  • Cell Line
  • Cell Nucleus / metabolism
  • Chromatin / chemistry*
  • Chromatin / ultrastructure
  • DNA / chemistry
  • DNA / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Immunoprecipitation
  • Interleukin-13 / genetics*
  • Interleukin-4 / genetics*
  • Lymphocyte Activation / genetics
  • Molecular Sequence Data
  • NFATC Transcription Factors / metabolism*
  • Nucleic Acid Conformation
  • Receptors, IgE / immunology
  • Th2 Cells / immunology*

Substances

  • CD28 Antigens
  • Chromatin
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Interleukin-13
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Receptors, IgE
  • Interleukin-4
  • DNA