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
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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CD4-Positive T-Lymphocytes / immunology*
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Cells, Cultured
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Humans
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Interleukin-2 / genetics*
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Jurkat Cells
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Lymphocyte Activation
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Mice
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Molecular Sequence Data
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Promoter Regions, Genetic
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RNA, Small Interfering / genetics
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transduction, Genetic
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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p300-CBP Transcription Factors / metabolism
Substances
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Bcl11b protein, mouse
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DNA-Binding Proteins
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Interleukin-2
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RNA, Small Interfering
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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Repressor Proteins
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Tumor Suppressor Proteins
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DNA
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p300-CBP Transcription Factors