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Distinct features of nucleolus-associated domains in mouse embryonic stem cells
Chromosoma ( IF 2.5 ) Pub Date : 2020-03-26 , DOI: 10.1007/s00412-020-00734-9
Aizhan Bizhanova 1 , Aimin Yan 1 , Jun Yu 1 , Lihua Julie Zhu 1 , Paul D Kaufman 1
Affiliation  

Heterochromatin in eukaryotic interphase cells frequently localizes to the nucleolar periphery (nucleolus-associated domains (NADs)) and the nuclear lamina (lamina-associated domains (LADs)). Gene expression in somatic cell NADs is generally low, but NADs have not been characterized in mammalian stem cells. Here, we generated the first genome-wide map of NADs in mouse embryonic stem cells (mESCs) via deep sequencing of chromatin associated with biochemically purified nucleoli. As we had observed in mouse embryonic fibroblasts (MEFs), the large type I subset of NADs overlaps with constitutive LADs and is enriched for features of constitutive heterochromatin, including late replication timing and low gene density and expression levels. Conversely, the type II NAD subset overlaps with loci that are not lamina-associated, but in mESCs, type II NADs are much less abundant than in MEFs. mESC NADs are also much less enriched in H3K27me3 modified regions than are NADs in MEFs. Additionally, comparision of MEF and mESC NADs revealed enrichment of developmentally regulated genes in cell-type-specific NADs. Together, these data indicate that NADs are a developmentally dynamic component of heterochromatin. These studies implicate association with the nucleolar periphery as a mechanism for developmentally regulated gene expression and will facilitate future studies of NADs during mESC differentiation.

中文翻译:

小鼠胚胎干细胞中核仁相关结构域的独特特征

真核间期细胞中的异染色质经常定位于核仁外围(核仁相关域 (NAD))和核层(层相关域 (LAD))。体细胞 NADs 中的基因表达通常较低,但尚未在哺乳动物干细胞中表征 NADs。在这里,我们通过对与生化纯化核仁相关的染色质进行深度测序,生成了小鼠胚胎干细胞 (mESC) 中 NAD 的第一个全基因组图谱。正如我们在小鼠胚胎成纤维细胞 (MEF) 中观察到的那样,NAD 的大 I 型子集与组成型 LAD 重叠,并且富含组成型异染色质的特征,包括复制延迟时间和基因密度和表达水平低。相反,II 型 NAD 子集与非椎板相关的基因座重叠,但在 mESCs 中,II 型 NADs 的含量远低于 MEFs。与 MEF 中的 NADs 相比,mESC NADs 在 H3K27me3 修饰区域中的含量也少得多。此外,MEF 和 mESC NADs 的比较揭示了细胞类型特异性 NADs 中发育调节基因的富集。总之,这些数据表明 NADs 是异染色质的发育动态成分。这些研究表明与核仁外周的关联是发育调控基因表达的一种机制,并将促进未来对 mESC 分化过程中 NAD 的研究。这些数据表明 NADs 是异染色质的发育动态成分。这些研究表明与核仁外周的关联是发育调控基因表达的一种机制,并将促进 mESC 分化过程中 NAD 的未来研究。这些数据表明 NADs 是异染色质的发育动态成分。这些研究表明与核仁外周的关联是发育调控基因表达的一种机制,并将促进未来对 mESC 分化过程中 NAD 的研究。
更新日期:2020-03-26
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