Department of Cell and Developmental Biology and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA 19104, USA.
Department of Medicine and Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA 19104, USA.
Nucleic Acids Res. 2021 Jun 21;49(11):6181-6195. doi: 10.1093/nar/gkab392.
Nuclear architecture influences gene regulation and cell identity by controlling the three-dimensional organization of genes and their distal regulatory sequences, which may be far apart in linear space. The genome is functionally and spatially segregated in the eukaryotic nucleus with transcriptionally active regions in the nuclear interior separated from repressive regions, including those at the nuclear periphery. Here, we describe the identification of a novel type of nuclear peripheral chromatin domain that is enriched for tissue-specific transcriptional enhancers. Like other chromatin at the nuclear periphery, these regions are marked by H3K9me2. But unlike the nuclear peripheral Lamina-Associated Domains (LADs), these novel, enhancer-rich domains have limited Lamin B interaction. We therefore refer to them as H3K9me2-Only Domains (KODs). In mouse embryonic stem cells, KODs are found in Hi-C-defined A compartments and feature relatively accessible chromatin. KODs are characterized by low gene expression and enhancers located in these domains bear the histone marks of an inactive or poised state. These results indicate that KODs organize a subset of inactive, tissue-specific enhancers at the nuclear periphery. We hypothesize that KODs may play a role in facilitating and perhaps constraining the enhancer-promoter interactions underlying spatiotemporal regulation of gene expression programs in differentiation and development.
核架构通过控制基因及其远端调控序列的三维组织来影响基因调控和细胞身份，这些序列在线性空间中可能相距甚远。真核细胞核内转录活跃区域与抑制区域（包括核周区域）在功能和空间上是分离的。在这里，我们描述了一种新型核周染色质结构域的鉴定，该结构域富含组织特异性转录增强子。与核周其他染色质一样，这些区域标记有 H3K9me2。但与核周 Lamina 相关结构域（LADs）不同，这些新型、富含增强子的结构域与 lamin B 的相互作用有限。因此，我们将它们称为 H3K9me2-Only 结构域（KODs）。在小鼠胚胎干细胞中，KODs 存在于 Hi-C 定义的 A 区室中，具有相对可及的染色质。KODs 的特征是低基因表达，并且位于这些结构域中的增强子具有失活或静止状态的组蛋白标记。这些结果表明，KODs 在核周组织了一组非活性的、组织特异性的增强子。我们假设 KODs 可能在促进和限制分化和发育过程中时空调节基因表达程序的增强子-启动子相互作用方面发挥作用。
