Martin Caden J, Oser Elizabeth A, Nagarajan Prabakaran, Popova Liudmila V, Sunkel Benjamin D, Stanton Benjamin Z, Parthun Mark R
Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, Ohio 43210, USA.
Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
Genome Res. 2025 Sep 2;35(9):1959-1974. doi: 10.1101/gr.280380.124.
A large fraction of the genome interacts with the nuclear periphery through lamina-associated domains (LADs), repressive regions which play an important role in genome organization and gene regulation across development. Despite much work, LAD structure and regulation are not fully understood, and a mounting number of studies have identified numerous genetic and epigenetic differences within LADs, demonstrating they are not a uniform group. Here, we profile lamin B1, CBX1 (also known as HP1B), H3K9me3, H3K9me2, H3K27me3, H3K14ac, H3K27ac, and H3K9ac in MEF cell lines derived from the same mouse colony, and cluster LADs based on the abundance and distribution of these features across LADs. We find that LADs fall into three groups, each enriched in a unique set of histone modifications and genomic features. Each group is defined by a different heterochromatin modification (H3K9me3, H3K9me2, or H3K27me3), suggesting that all three of these marks play important roles in regulation of LAD chromatin and potentially of lamina association. We also discover unique features of LAD borders, including a LAD border-specific enrichment of H3K14ac. These results reveal important distinctions between LADs and highlight the rich diversity and complexity in LAD structure and regulatory mechanisms.
基因组的很大一部分通过核纤层相关结构域(LADs)与核周相互作用,这些抑制性区域在整个发育过程中的基因组组织和基因调控中发挥着重要作用。尽管进行了大量研究,但LAD的结构和调控仍未完全了解,并且越来越多的研究已经在LADs中发现了许多遗传和表观遗传差异,表明它们不是一个统一的群体。在这里,我们对来自同一小鼠群体的MEF细胞系中的核纤层蛋白B1、CBX1(也称为HP1B)、H3K9me3、H3K9me2、H3K27me3、H3K14ac、H3K27ac和H3K9ac进行了分析,并根据这些特征在LADs中的丰度和分布对LADs进行聚类。我们发现LADs分为三组,每组都富含一组独特的组蛋白修饰和基因组特征。每组由不同的异染色质修饰(H3K9me3、H3K9me2或H3K27me3)定义,这表明所有这三种标记在LAD染色质的调控以及潜在的核纤层关联中都发挥着重要作用。我们还发现了LAD边界的独特特征,包括H3K14ac在LAD边界处的特异性富集。这些结果揭示了LADs之间的重要区别,并突出了LAD结构和调控机制的丰富多样性和复杂性。
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