Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis.
Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis.
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发表时间：
1994-04
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影响因子：
8
通讯作者：
Te-Chung Lee;Yue Zhang;R. Schwartz
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作者：
Te-Chung Lee;Yue Zhang;R. Schwartz
癌基因表达通常与肌发生中的终末细胞分化不相容。我们提出的证据表明，这种不相容性可能部分是由 Kruppel 相关锌指 YY1（以前称为 F-ACT1）的双重活性引起的，该活性可差异调节癌基因和肌肉特异性基因表达。 c-myc 和骨骼 α-肌动蛋白基因启动子含有 YY1 结合位点，被认为可作为正顺式作用元件或负顺式作用元件。通过用溴脱氧尿苷（BrdU）处理原代成肌细胞来控制YY1的细胞内水平，抑制肌生成并增加YY1蛋白含量，或者通过转染YY1 cDNA表达载体，我们表明它可以同时分别抑制和激活骨骼α-肌动蛋白和c-myc基因的表达。 YY1 的反式抑制活性仅取决于其 C 端锌指区域（氨基酸 297-407），而其反式激活功能则需要额外的 N 端结构域（氨基酸 1-90），该结构域通常隐藏在全长蛋白中。我们认为，增殖的成肌细胞中高水平的 YY1 可能有助于维持 c-myc 表达并抑制肌肉肌动蛋白表达，然后可以通过下调 YY1 活性以促进肌生成而逐渐逆转这种情况。
Oncogene expression is generally incompatible with terminal cell differentiation as in myogenesis. We present evidence that this incompatibility can be caused in part by the dual activity of a Kruppel-related zinc finger, YY1 (formerly F-ACT1), in differentially regulating oncogene and muscle-specific gene expression. The c-myc and skeletal alpha-actin gene promoters contain YY1 binding sites thought to act either as positive or negative cis-acting elements. Through manipulating the intracellular level of YY1 by treating primary myoblasts with bromodeoxyuridine (BrdU), which inhibited myogenesis and increased the YY1 protein content, or by transfecting YY1 cDNA expression vector, we show that it can simultaneously inhibit and activate expression of the skeletal alpha-actin and c-myc genes, respectively. The transrepression activity of YY1 solely depends on its C-terminal zinc finger region (amino acids 297-407) while its transactivation function requires an additional N-terminal domain (amino acids 1-90) normally masked in the full-length protein. We propose that the high level of YY1 in proliferating myoblasts might serve to maintain c-myc expression and suppress muscle actin expression, which can then be gradually reversed by downregulating YY1 activity toward myogenesis.