London Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada.
Department of Biochemistry, Western University, London, Ontario, Canada.
Mol Cell Biol. 2020 Jan 3;40(2). doi: 10.1128/MCB.00452-19.
Interphase chromosomes are organized into topologically associated domains in order to establish and maintain integrity of transcriptional programs that remain poorly understood. Here, we show that condensin II and TFIIIC are recruited to bidirectionally transcribed promoters by a mechanism that is dependent on the retinoblastoma (RB) protein. Long-range chromosome contacts are disrupted by loss of condensin II loading, which leads to altered expression at bidirectional gene pairs. This study demonstrates that mammalian condensin II functions to organize long-range chromosome contacts and regulate transcription at specific genes. In addition, RB dependence of condensin II suggests that widespread misregulation of chromosome contacts and transcriptional alterations are a consequence of RB mutation.
间期染色体被组织成拓扑关联域,以建立和维持转录程序的完整性,而这些程序仍知之甚少。在这里,我们表明,有丝分裂后期促进复合物 II 和 TFIIIC 通过一种依赖视网膜母细胞瘤(RB)蛋白的机制被募集到双向转录启动子。长距离染色体接触被有丝分裂后期促进复合物 II 加载的缺失所破坏,这导致双向基因对的表达改变。这项研究表明,哺乳动物有丝分裂后期促进复合物 II 的功能是组织长距离染色体接触,并调节特定基因的转录。此外,有丝分裂后期促进复合物 II 对 RB 的依赖性表明,染色体接触和转录改变的广泛失调是 RB 突变的结果。