A negative regulatory element-dependent inhibitory role of ITF2B on IL-2 receptor alpha gene.
Despite the fact that the negative regulatory element (NRE) within the upstream regulatory region of human IL-2 receptor alpha (IL-2Ralpha) gene has been identified two decades ago, mechanisms of the NRE function on the gene are hitherto unknown. In this paper, we report for the first time that the immunoglobulin transcription factor 2B (ITF2B) encoded by transcription factor 4 (TCF4) gene is a NRE binding protein. The full-length TCF4 cDNA clone was obtained from a HTLV-1 transformed human peripheral T cell MACHERMAKER cDNA library with NRE as the bait in yeast one-hybrid system. The NRE binding ability of ITF2B was further confirmed in chromatin-immunoprecipitation assay. Competitive RT-PCR-based promoter activity assay showed that over-expression of ITF2B protein inhibited the expression of IL-2Ralpha gene in Jurkat cells in an NRE-dependent manner. The function of ITF2B on the inhibition of both the IL-2Ralpha and the 5'LTR activity of HIV-1 shed light on the essence of NRE binding protein as a potential target for immune therapy and treatment in AIDS patients.
Lu
Yu
Y
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Sheng
De-Qiao
DQ
Mo
Zhi-Cheng
ZC
Li
Hong-Fan
HF
Wu
Ning-Hua
NH
Shen
Yu-Fei
YF
D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015139:Blotting, Southern; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D006801:Humans; D047468:Immunoprecipitation; D053645:Interleukin-2 Receptor alpha Subunit; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*; D051820:TCF Transcription Factors; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D051820:TCF Transcription Factors; C532096:TCF4 protein, human; C544894:TCF7L2 protein, human; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors