Hinkley C, Perry M
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Mol Cell Biol. 1992 Oct;12(10):4400-11. doi: 10.1128/mcb.12.10.4400-4411.1992.
The ubiquitously expressed transcription factor Oct-1 and several other members of the POU domain protein family bind to a site, termed the octamer motif, that functions in the promoter and enhancer regions of a variety of genes expressed under diverse conditions. An octamer motif present in a conserved histone H2B-specific promoter element is required for S-phase-specific transcription of mammalian histone H2B genes in cultured cells. We have previously shown that the octamer motif in a Xenopus histone H2B gene promoter was inactive in nondividing frog oocytes. Here we show that the octamer motif, in addition to regulatory elements (TATAA, CCAAT, and ATF motifs) that are active in oocytes, is required for maximal H2B gene transcription in developing frog embryos. Factors binding to each of the H2B upstream promoter elements are present in oocytes and increase slightly in abundance during early development. The activity of the H2B octamer motif in embryos is not specifically associated with increased binding by Oct-1 or the appearance of novel octamer-binding proteins but requires the presence of an intact CCAAT motif. Our results indicate that synergistic interactions among promoter-bound factors are important for octamer-dependent H2B transcription. We suggest that the activity of the H2B promoter is regulated primarily by changes in the interactions between proteins already bound to the promoter rather than by alterations in their intrinsic abilities to bind DNA.
普遍表达的转录因子Oct-1以及POU结构域蛋白家族的其他几个成员与一个称为八聚体基序的位点结合,该位点在多种条件下表达的各种基因的启动子和增强子区域发挥作用。培养细胞中哺乳动物组蛋白H2B基因的S期特异性转录需要保守的组蛋白H2B特异性启动子元件中存在的八聚体基序。我们之前已经表明,非洲爪蟾组蛋白H2B基因启动子中的八聚体基序在未分裂的蛙卵母细胞中无活性。在这里我们表明,除了在卵母细胞中具有活性的调控元件(TATAA、CCAAT和ATF基序)外,八聚体基序对于发育中的蛙胚胎中H2B基因的最大转录也是必需的。与每个H2B上游启动子元件结合的因子存在于卵母细胞中,并且在早期发育过程中丰度略有增加。胚胎中H2B八聚体基序的活性与Oct-1结合增加或新的八聚体结合蛋白的出现没有特异性关联,但需要完整的CCAAT基序的存在。我们的结果表明,启动子结合因子之间的协同相互作用对于八聚体依赖性H2B转录很重要。我们认为,H2B启动子的活性主要通过已结合到启动子上的蛋白质之间相互作用的变化来调节,而不是通过它们结合DNA的内在能力的改变来调节。