Allen R D, Kim H K, Sarafova S D, Siu G
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Mol Cell Biol. 2001 May;21(9):3071-82. doi: 10.1128/MCB.21.9.3071-3082.2001.
Expression of the CD4 gene is tightly controlled throughout thymopoiesis. The downregulation of CD4 gene expression in CD4(-) CD8(-) and CD4(-) CD8(+) T lymphocytes is controlled by a transcriptional silencer located in the first intron of the CD4 locus. Here, we determine that the c-Myb transcription factor binds to a functional site in the CD4 silencer. As c-Myb is also required for CD4 promoter function, these data indicate that depending on the context, c-Myb plays both positive and negative roles in the control of CD4 gene expression. Interestingly, a second CD4 silencer-binding factor, HES-1, binds to c-Myb in vivo and induces it to become a transcriptional repressor. We propose that the recruitment of HES-1 and c-Myb to the silencer leads to the formation of a multifactor complex that induces silencer function and repression of CD4 gene expression.
CD4基因的表达在整个胸腺细胞生成过程中受到严格控制。CD4（-）CD8（-）和CD4（-）CD8（+）T淋巴细胞中CD4基因表达的下调由位于CD4基因座第一个内含子中的转录沉默子控制。在此，我们确定c-Myb转录因子与CD4沉默子中的一个功能位点结合。由于CD4启动子功能也需要c-Myb，这些数据表明，根据具体情况，c-Myb在CD4基因表达的控制中发挥着正负双重作用。有趣的是，另一种与CD4沉默子结合的因子HES-1在体内与c-Myb结合，并诱导其成为转录抑制因子。我们提出，HES-1和c-Myb被招募到沉默子导致形成一个多因子复合物，该复合物诱导沉默子功能并抑制CD4基因表达。
