Department of MCD Biology, University of California, Santa Cruz, California, USA.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Mol Cell Biol. 2019 Apr 2;39(8). doi: 10.1128/MCB.00432-18. Print 2019 Apr 15.
The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the roles of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacked any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromatin architecture or chromosome tethering and mobility. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long-range heterochromatin clustering with concomitant effects on gene silencing. We propose that the tDNAs primarily affect local chromatin structure, which results in effects on long-range chromosome architecture.
基因组以有序、非随机的方式进行包装和组织，特定的染色质片段与核亚结构接触，以介导这种组织。tRNA 基因（tDNAs）是转录因子和结构蛋白的结合位点，被认为在基因组的组织中发挥重要作用。在这项研究中，我们通过编辑一条染色体，使其缺乏任何 tDNAs，从而研究 tDNAs 在基因组组织和染色体功能中的作用。令人惊讶的是，我们对这条 tDNA 缺失染色体的分析表明，tDNAs 的缺失不会严重影响染色质结构或染色体连接和移动。然而，tDNAs 的缺失会影响局部核小体定位以及 SMC 蛋白在这些基因座上的结合。tDNAs 的缺失还会导致着丝粒聚类的变化，并减少长距离异染色质聚类的频率，从而影响基因沉默。我们提出 tDNAs 主要影响局部染色质结构，从而影响长距离染色体结构。
