BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes.
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.
Cismasiu
Valeriu B
VB
Center for Cell Biology and Cancer Research (MC-165), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Ghanta
Sailaja
S
Duque
Javier
J
Albu
Diana I
DI
Chen
Hong-Mei
HM
Kasturi
Rohini
R
Avram
Dorina
D
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; D050880:p300-CBP Transcription Factors