Department of Biochemistry/Biophysics, Texas A&M University, College Station, Texas, United States of America.
PLoS One. 2011 Jan 20;6(1):e16401. doi: 10.1371/journal.pone.0016401.
In the repeat array of ribosomal DNA (rDNA), only about half of the genes are actively transcribed while the others are silenced. In arthropods, transposable elements interrupt a subset of genes, often inactivating transcription of those genes. Little is known about the establishment or separation of juxtaposed active and inactive chromatin domains, or preferential inactivation of transposable element interrupted genes, despite identity in promoter sequences. CTCF is a sequence-specific DNA binding protein which is thought to act as a transcriptional repressor, block enhancer-promoter communication, and delimit juxtaposed domains of active and inactive chromatin; one or more of these activities might contribute to the regulation of this repeated gene cluster. In support of this hypothesis, we show that the Drosophila nucleolus contains CTCF, which is bound to transposable element sequences within the rDNA. Reduction in CTCF gene activity results in nucleolar fragmentation and reduced rDNA silencing, as does disruption of poly-ADP-ribosylation thought to be necessary for CTCF nucleolar localization. Our data establish a role for CTCF as a component necessary for proper control of transposable element-laden rDNA transcription and nucleolar stability.
在核糖体 DNA(rDNA)的重复序列中，只有大约一半的基因是活跃转录的，而其他基因则处于沉默状态。在节肢动物中，转座元件会中断一部分基因，通常会使这些基因的转录失活。尽管启动子序列相同，但关于相邻的活跃和非活跃染色质域的建立或分离，或优先失活转座元件中断的基因，人们知之甚少。CTCF 是一种序列特异性 DNA 结合蛋白，被认为是一种转录抑制因子，阻止增强子-启动子通讯，并限制活跃和非活跃染色质的相邻域；这些活性中的一种或多种可能有助于调节这个重复基因簇。为了支持这一假说，我们表明果蝇核仁中含有 CTCF，它与 rDNA 中的转座元件序列结合。CTCF 基因活性的降低会导致核仁碎片化和 rDNA 沉默减少，而聚 ADP-核糖基化的破坏也会导致核仁定位所必需的 CTCF，这也会导致核仁碎片化和 rDNA 沉默减少。我们的数据确立了 CTCF 作为一个必要的组成部分，它对于正确控制富含转座元件的 rDNA 转录和核仁稳定性是必需的。
