Gierman Hinco J, Indemans Mireille H G, Koster Jan, Goetze Sandra, Seppen Jurgen, Geerts Dirk, van Driel Roel, Versteeg Rogier
Department of Human Genetics, Academic Medical Centre, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
Genome Res. 2007 Sep;17(9):1286-95. doi: 10.1101/gr.6276007. Epub 2007 Aug 10.
Transcription factor complexes bind to regulatory sequences of genes, providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 80-90 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 different chromosomal positions obtain expression levels that correspond to the activity of the domains of integration. These domains are up to 80 genes long and can exert an eightfold effect on the expression levels of integrated genes. 3D-FISH shows that active domains of integration have a more open chromatin structure than integration domains with weak activity. These results reveal a novel domain-wide regulatory mechanism that, together with transcription factors, exerts a dual control over gene transcription.
转录因子复合物与基因的调控序列结合，提供了一个个体表达调控系统。不同转录因子的靶标通常分布于整个基因组，并不成簇。然而，高表达和低表达基因确实会在平均大小为80 - 90个基因的不同染色体结构域中聚类。因此，我们不禁要问，除了转录因子之外，是否还存在作用于染色体结构域的另一层次的基因表达调控。在此我们表明，整合在90个不同染色体位置的相同绿色荧光蛋白（GFP）报告构建体获得的表达水平与整合结构域的活性相对应。这些结构域长达80个基因，可对整合基因的表达水平产生八倍的影响。三维荧光原位杂交（3D - FISH）显示，活跃的整合结构域比活性较弱的整合结构域具有更开放的染色质结构。这些结果揭示了一种新的全结构域调控机制，该机制与转录因子一起对基因转录发挥双重控制作用。
