Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Department of Biochemistry and Molecular Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Sci Adv. 2017 Jun 21;3(6):e1700191. doi: 10.1126/sciadv.1700191. eCollection 2017 Jun.
Structural maintenance of chromosome complexes, such as cohesin, have been implicated in a wide variety of chromatin-dependent functions such as genome organization, replication, and gene expression. How these complexes find their sites of association and affect local chromosomal processes is not well understood. We report that condensin II, a complex distinct from cohesin, physically interacts with TFIIIC, and they both colocalize at active gene promoters in the mouse and human genomes, facilitated by interaction between NCAPD3 and the epigenetic mark H3K4me3. Condensin II is important for maintaining high levels of expression of the histone gene clusters as well as the interaction between these clusters in the mouse genome. Our findings suggest that condensin II is anchored to the mammalian genome by a combination of H3K4me3 and the sequence-specific binding of TFIIIC, and that condensin supports the expression of active gene-dense regions found at the boundaries of topological domains. Together, our results support a working model in which condensin II contributes to topological domain boundary-associated gene activity in the mammalian genome.
染色体复合物的结构维持,如黏合蛋白,与多种依赖染色质的功能有关,如基因组组织、复制和基因表达。这些复合物如何找到它们的结合位点并影响局部染色体过程尚不清楚。我们报告说,与黏合蛋白不同的 condensin II 复合物与 TFIIIC 发生物理相互作用,并且它们都在活跃的基因启动子处共定位在小鼠和人类基因组中,这得益于 NCAPD3 与表观遗传标记 H3K4me3 之间的相互作用。condensin II 对于维持组蛋白基因簇的高水平表达以及在小鼠基因组中这些簇之间的相互作用非常重要。我们的发现表明,condensin II 通过 H3K4me3 和 TFIIIC 的序列特异性结合锚定在哺乳动物基因组上,并且 condensin 支持在拓扑结构域边界处发现的活性基因密集区的表达。总之,我们的结果支持了一个工作模型,即 condensin II 有助于哺乳动物基因组中拓扑结构域边界相关基因活性。