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Abstract：
How repetitive elements, epigenetic modifications, and architectural proteins interact ensuring proper genome expression remains poorly understood. Here, we report regulatory mechanisms unveiling a central role of Alu elements (AEs) and RNA polymerase III transcription factor C (TFIIIC) in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of AEs pre-marked by the activity-dependent neuroprotector homeobox Protein (ADNP) and located near cell-cycle genes recruits TFIIIC, which alters their chromatin accessibility by direct acetylation of histone H3 lysine-18 (H3K18). This facilitates the contacts of AEs with distant CTCF sites near promoter of other cell-cycle genes, which also become hyperacetylated at H3K18. These changes ensure basal transcription of cell-cycle genes and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor regulates 3D genome folding and expression.
摘要：
如何重复元素，表观遗传修饰,和建筑蛋白相互作用，确保正确的基因组表达仍然知之甚少。这里,我们报告的调节机制揭示了Alu元件(AEs)和RNA聚合酶III转录因子C(TFIIIC)在通过染色质循环和组蛋白乙酰化进行基因组结构和功能调节中的重要作用.血清剥夺后，由活性依赖性神经保护者同源异型盒蛋白（ADNP）预先标记并位于细胞周期基因附近的AE子集招募TFIIIC，通过组蛋白H3赖氨酸-18（H3K18）的直接乙酰化改变其染色质可及性。这促进了AEs与其他细胞周期基因启动子附近的远处CTCF位点的接触，在H3K18也被高度乙酰化。这些变化确保了细胞周期基因的基础转录，并且对于血清再暴露后的再激活至关重要。我们的研究揭示了一般转录因子对AE的表观遗传状态的直接操纵如何调节3D基因组折叠和表达。
