Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo, Japan.
J Cell Biol. 2019 Jan 7;218(1):134-149. doi: 10.1083/jcb.201805003. Epub 2018 Nov 5.
The centromere is an important genomic locus for chromosomal segregation. Although the centromere is specified by sequence-independent epigenetic mechanisms in most organisms, it is usually composed of highly repetitive sequences, which associate with heterochromatin. We have previously generated various chicken DT40 cell lines containing differently positioned neocentromeres, which do not contain repetitive sequences and do not associate with heterochromatin. In this study, we performed systematic 4C analysis using three cell lines containing differently positioned neocentromeres to identify neocentromere-associated regions at the 3D level. This analysis reveals that these neocentromeres commonly associate with specific heterochromatin-rich regions, which were distantly located from neocentromeres. In addition, we demonstrate that centromeric chromatin adopts a compact structure, and centromere clustering also occurs in vertebrate interphase nuclei. Interestingly, the occurrence of centromere-heterochromatin associations depend on CENP-H, but not CENP-C. Our analyses provide an insight into understanding the 3D architecture of the genome, including the centromeres.
着丝粒是染色体分离的重要基因组位点。尽管在大多数生物体中，着丝粒是由序列非依赖性的表观遗传机制决定的，但它通常由高度重复的序列组成，这些序列与异染色质相关联。我们之前已经生成了各种含有不同定位的新着丝粒的鸡 DT40 细胞系，这些新着丝粒不含有重复序列，也不与异染色质相关联。在这项研究中，我们使用三个含有不同定位的新着丝粒的细胞系进行了系统的 4C 分析，以在 3D 水平上鉴定与新着丝粒相关的区域。该分析表明，这些新着丝粒通常与远离新着丝粒的特定富含异染色质的区域相关联。此外，我们证明了着丝粒染色质采用紧凑的结构，并且着丝粒聚类也发生在脊椎动物间期核中。有趣的是，着丝粒-异染色质的关联的发生取决于 CENP-H，但不取决于 CENP-C。我们的分析为理解包括着丝粒在内的基因组的 3D 结构提供了一个视角。
