BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes

Blood. 2006 Oct 15;108(8):2695-702. doi: 10.1182/blood-2006-05-021790. Epub 2006 Jun 29.

Abstract

BCL11A and BCL11B are transcriptional regulators important for lymphopoiesis and previously associated with hematopoietic malignancies. Ablation of the mouse Bcl11b locus results in failure to generate double-positive thymocytes, implicating a critical role of Bcl11b in T-cell development. However, BCL11B is also expressed in CD4+ T lymphocytes, both in resting and activated states. Here we show both in transformed and primary CD4+ T cells that BCL11B participates in the control of the interleukin-2 (IL2) gene expression following activation through T-cell receptor (TCR). BCL11B augments expression from the IL2 promoter through direct binding to the US1 site. In addition, BCL11B associates with the p300 coactivator in CD4+ T cells activated through TCR, which may account for its transcriptional activation function. These results provide the first evidence that BCL11B, originally described as a transcriptional repressor, activates transcription of a target gene in the context of T-cell activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interleukin-2 / genetics*
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transduction, Genetic
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • p300-CBP Transcription Factors / metabolism

Substances

  • Bcl11b protein, mouse
  • DNA-Binding Proteins
  • Interleukin-2
  • RNA, Small Interfering
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • DNA
  • p300-CBP Transcription Factors