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首页> 外文期刊>The Journal of biological chemistry >Ribosomal RNA Gene Transcription Mediated by the Master Genome Regulator Protein CCCTC-binding Factor (CTCF) Is Negatively Regulated by the Condensin Complex
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Ribosomal RNA Gene Transcription Mediated by the Master Genome Regulator Protein CCCTC-binding Factor (CTCF) Is Negatively Regulated by the Condensin Complex

机译：由母系稳压蛋白CCCTC结合因子（CTCF）介导的核糖体RNA基因转录被凝聚络合物负调节

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摘要

CCCTC-binding factor (CTCF) is a ubiquitously expressed “master weaver” and plays multiple functions in the genome, including transcriptional activation/repression, chromatin insulation, imprinting, X chromosome inactivation, and high-order chromatin organization. It has been shown that CTCF facilitates the recruitment of the upstream binding factor onto ribosomal DNA (rDNA) and regulates the local epigenetic state of rDNA repeats. However, the mechanism by which CTCF modulates rRNA gene transcription has not been well understood. Here we found that wild-type CTCF augments the pre-rRNA level, cell size, and cell growth in cervical cancer cells. In contrast, RNA interference-mediated knockdown of CTCF reduced pre-rRNA transcription. CTCF positively regulates rRNA gene transcription in a RNA polymerase I-dependent manner. We identified an RRGR motif as a putative nucleolar localization sequence in the C-terminal region of CTCF that is required for activating rRNA gene transcription. Using mass spectrometry, we identified SMC2 and SMC4, two subunits of condensin complexes that interact with CTCF. Condensin negatively regulates CTCF-mediated rRNA gene transcription. Knockdown of SMC2 expression significantly facilitates the loading of CTCF and the upstream binding factor onto the rDNA locus and increases histone acetylation across the rDNA locus. Taken together, our study suggests that condensin competes with CTCF in binding to a specific rDNA locus and negatively regulates CTCF-mediated rRNA gene transcription.
机译：CCCTC结合因子（CTCF）是普遍地表达的“主编织器”，并在基因组中起多种功能，包括转录激活/抑制，染色质绝缘，印迹，X染色体灭活，以及高阶染色质组织。已经表明，CTCF促进了上游结合因子募集到核糖体DNA（RDNA）上，并调节RDNA重复的局部表观遗传状态。然而，CTCF调节RRNA基因转录的机制尚未得到很好的理解。在这里，我们发现野生型CTCF增加了宫颈癌细胞中的rRNA水平，细胞尺寸和细胞生长。相比之下，CTCF的RNA干扰介导的敲低rRNA转录。 CTCF以RNA聚合酶I依赖性方式呈正常调节RRNA基因转录。我们将RRGR基序作为激活RRNA基因转录所需的CTCF的C末端区域中的推定核仁定位序列。使用质谱法，我们鉴定了SMC2和SMC4，与CTCF相互作用的夹杂物复合物的两个亚基。夹杂物负调节CTCF介导的RRNA基因转录。 SMC2表达的敲低显着促进CTCF和上游结合因子的加载到RDNA基因座上，并在RDNA基因座上增加组蛋白乙酰化。我们的研究表明，凝结凝结与CTCF与特定RDNA基因座结合并负调节CTCF介导的RRNA基因转录。

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