首页> 外文期刊>Genomics >Transgenes encompassing dual-promoter CpG islands from the human TBP and HNRPA2B1 loci are resistant to heterochromatin-mediated silencing.
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Transgenes encompassing dual-promoter CpG islands from the human TBP and HNRPA2B1 loci are resistant to heterochromatin-mediated silencing.

机译:包含来自人TBP和HNRPA2B1基因座的双启动子CpG岛的转基因对异染色质介导的沉默具有抗性。

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摘要

The genetic elements that are responsible for establishing a transcriptionally competent, open chromatin structure at a region of the genome that consists only of ubiquitously expressed, housekeeping genes are currently unknown. We demonstrate for the first time through functional analysis in stably transfected tissue culture cells that transgenes containing methylation-free CpG islands spanning the dual divergently transcribed promoters from the human TATA binding protein (TBP)-proteasome component-B1 (PSMB1) and heterogeneous nuclear ribonucleoprotein A2/B1 (HNRPA2B1)-heterochromatin protein 1Hs-gamma (chromobox homolog 3, CBX3) gene loci are sufficient to prevent transcriptional silencing and a variegated expression pattern when integrated within centromeric heterochromatin. In addition, only transgene constructs extending over both the HNRPA2B1 and the CBX3 promoters, and not the HNRPA2B1 promoter alone, were able to confer high and stable long-term EGFP reporter gene expression. These observationssuggest that methylation-free CpG islands associated with dual, divergently transcribed promoters possess an independent dominant chromatin opening function and may therefore be major determinants in establishing and maintaining a region of open chromatin at housekeeping gene loci.
机译:目前尚不清楚负责在仅由普遍表达的管家基因组成的基因组区域建立转录能力,开放染色质结构的遗传元件。我们首次通过功能分析在稳定转染的组织培养细胞中证明了该转基因包含不含甲基化的CpG岛的转基因,该岛跨越了来自人TATA结合蛋白(TBP)-蛋白酶体组分-B1(PSMB1)和异质核糖核糖核蛋白的双重发散转录的启动子当整合到着丝粒异染色质中时,A2 / B1(HNRPA2B1)-异染色质蛋白1Hs-γ(染色体框同源物3,CBX3)基因位点足以防止转录沉默和多样化的表达模式。此外,只有延伸到HNRPA2B1和CBX3启动子上的转基因构建体,而不是单独的HNRPA2B1启动子,才能够赋予高而稳定的长期EGFP报告基因表达。这些观察结果表明,与双重,发散转录的启动子相关的无甲基化的CpG岛具有独立的显性染色质开放功能,因此可能是在管家基因位点建立和维持开放性染色质区域的主要决定因素。

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