DNA satellite and chromatin organization at house mouse centromeres and pericentromeres.
DNA satellite and chromatin organization at house mouse centromeres and pericentromeres.
复制标题
家鼠着丝粒和着丝粒周围的 DNA 卫星和染色质组织。
DOI：
10.1101/2023.07.18.549612
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Thakur,Jitendra
中科院分区：
文献类型：
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作者：
Packiaraj,Jenika;Thakur,Jitendra
着丝粒对于有丝分裂和减数分裂过程中染色体的忠实分离至关重要。然而，由于测序和组装重复基因组区域的挑战，人们对小鼠着丝粒和着丝粒周围的卫星 DNA 和染色质的组织知之甚少。使用最近获得的 C57BL/6 菌株的 PacBio 长读长测序数据和染色质分析，我们发现与之前报道的高度同质性相反，着丝粒和近着丝粒卫星显示出不同的序列和组织。我们发现着丝粒小卫星和着丝粒周围主要卫星都表现出阵列内和阵列之间的序列变异。虽然大多数阵列是连续的，但很大一部分散布着非卫星序列，包括转座元件。此外，我们使用染色质免疫沉淀测序 (ChIP-seq) 研究了着丝粒和着丝粒周围的 CENP-A 和 H3K9me3 染色质组织。我们发现CENP-A和H3K9me3染色质分别在着丝粒和周着丝粒区域的占据与这些区域的序列丰度和同质性增加相关。此外，着丝粒区域的转座元件不是功能着丝粒的一部分，因为它们缺乏 CENP-A 富集。最后，我们发现虽然 H3K9me3 核小体在主要卫星阵列上显示出良好的定相组织，但小卫星阵列上的 CENP-A 核小体缺乏定相组织。有趣的是，同质类主要卫星也对 CENP-A 和 H3K27me3 核小体进行定相，表明核小体定相是同质主要卫星的固有特性。总的来说，我们的研究结果表明，以前被认为高度同质的家鼠着丝粒和着丝粒周围在卫星序列、组织和染色质结构方面表现出显着的多样性。
Centromeres are essential for faithful chromosome segregation during mitosis and meiosis. However, the organization of satellite DNA and chromatin at mouse centromeres and pericentromeres is poorly understood due to the challenges of sequencing and assembling repetitive genomic regions. Using recently available PacBio long-read sequencing data from the C57BL/6 strain and chromatin profiling, we found that contrary to the previous reports of their highly homogeneous nature, centromeric and pericentromeric satellites display varied sequences and organization. We find that both centromeric minor satellites and pericentromeric major satellites exhibited sequence variations within and between arrays. While most arrays are continuous, a significant fraction is interspersed with non-satellite sequences, including transposable elements. Additionally, we investigated CENP-A and H3K9me3 chromatin organization at centromeres and pericentromeres using Chromatin immunoprecipitation sequencing (ChIP-seq). We found that the occupancy of CENP-A and H3K9me3 chromatin at centromeric and pericentric regions, respectively, is associated with increased sequence abundance and homogeneity at these regions. Furthermore, the transposable elements at centromeric regions are not part of functional centromeres as they lack CENP-A enrichment. Finally, we found that while H3K9me3 nucleosomes display a well-phased organization on major satellite arrays, CENP-A nucleosomes on minor satellite arrays lack phased organization. Interestingly, the homogeneous class of major satellites phase CENP-A and H3K27me3 nucleosomes as well, indicating that the nucleosome phasing is an inherent property of homogeneous major satellites. Overall, our findings reveal that house mouse centromeres and pericentromeres, which were previously thought to be highly homogenous, display significant diversity in satellite sequence, organization, and chromatin structure.