Pennetta G, Pauli D
Department of Zoology and Animal Biology, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
Dev Genes Evol. 1998 Nov;208(9):531-6. doi: 10.1007/s004270050212.
Expression of many mammalian genes is activated by the binding of heterodimers of the Myc and Max proteins to specific DNA sequences called the E-boxes. Transcription of the same genes is repressed upon binding to the same sequences of complexes composed of Max, Mad/Mxi1, the co-repressors Sin3 and N-CoR, and the histone deacetylase Rpd3. Max-Mad/Mxi1 heterodimers, which bind to E-boxes in absence of co-repressors, do not inhibit gene expression simply by competition with Myc-Max heterodimers, but require Sin3 and Rpd3 for efficient repression of transcription. We have cloned a Drosophila homolog of Sin3 (dSin3) and found it to be ubiquitously expressed during embryonic development. Yeast, mouse and Drosophila proteins share six blocks of strong homologies, including four potential paired amphipathic helix domains. In addition, the domain of binding to the histone deacetylase Rpd3 is strongly conserved. Null mutations cause recessive embryonic lethality.
许多哺乳动物基因的表达是通过Myc和Max蛋白的异二聚体与称为E盒的特定DNA序列结合而被激活的。当与由Max、Mad/Mxi1、共抑制因子Sin3和N-CoR以及组蛋白脱乙酰酶Rpd3组成的复合物的相同序列结合时，相同基因的转录受到抑制。在没有共抑制因子的情况下与E盒结合的Max-Mad/Mxi1异二聚体，并非仅仅通过与Myc-Max异二聚体竞争来抑制基因表达，而是需要Sin3和Rpd3才能有效抑制转录。我们克隆了果蝇Sin3的同源物（dSin3），并发现它在胚胎发育过程中普遍表达。酵母、小鼠和果蝇的蛋白质共有六个高度同源的区域，包括四个潜在的成对两亲性螺旋结构域。此外，与组蛋白脱乙酰酶Rpd3结合的结构域高度保守。无效突变会导致隐性胚胎致死。
