Abstract:
Transcription factors (TFs) bind DNA in a sequence-specific manner and are generally cell type-specific factors and/or developmental master regulators. In contrast, general TFs (GTFs) are part of very large protein complexes and serve for RNA polymerases\' recruitment to promoter sequences, generally in a cell type-independent manner. Whereas, several TFs have been proven to serve as anchors for the 3D genome organization, the role of GTFs in genome architecture have not been carefully explored. Here, we used ChIP-seq and Hi-C data to depict the role of TFIIIC, one of the RNA polymerase III GTFs, in 3D genome organization. We find that TFIIIC genome occupancy mainly occurs at specific regions, which largely correspond to Alu elements; other characteristic classes of repetitive elements (REs) such as MIR, FLAM-C and ALR/alpha are also found depending on the cell\'s developmental origin. The analysis also shows that TFIIIC-enriched regions are involved in cell type-specific DNA looping, which does not depend on colocalization with the master architectural protein CTCF. This work extends previous knowledge on the role of TFIIIC as a bona fide genome organizer whose action participates in cell type-dependent 3D genome looping via binding to REs.
摘要:
转录因子(TF)以序列特异性方式结合DNA,并且通常是细胞类型特异性因子和/或发育主调节因子。相比之下,一般TFs(GTFs)是非常大的蛋白质复合物的一部分,用于RNA聚合酶募集到启动子序列,通常以细胞类型独立的方式。然而,几个TF已经被证明可以作为3D基因组组织的锚,GTFs在基因组结构中的作用尚未得到仔细研究。这里,我们使用ChIP-seq和Hi-C数据来描述TFIIC的作用,RNA聚合酶IIIGTF之一,在3D基因组组织中。我们发现TFIIIC基因组占用主要发生在特定区域,很大程度上对应于Alu元素;重复元素(RE)的其他特征类,如MIR,根据细胞的发育起源,还发现了FLAM-C和ALR/alpha。分析还表明,TFIIIC富集区域参与细胞类型特异性DNA循环,这不依赖于与主结构蛋白CTCF的共定位。这项工作扩展了关于TFIIIC作为真正的基因组组织者的作用的先前知识,其作用通过与RE结合参与细胞类型依赖性3D基因组循环。