加州大学Daniel A. Lim团队近日取得一项新成果。经过不懈努力，他们揭示了亚核基因组区隔化控制二价染色质活性。这一研究成果发表在2026年7月22日出版的国际学术期刊《自然》上。

在这里，该课题组研究人员生成了从妊娠中期人类皮层分离的神经源性谱系细胞中与层状和斑点的基因组相互作用的高分辨率地图，确定了亚核基因组区隔化、染色质状态和转录之间的密切联系。在皮层神经发生过程中，亚核基因组区隔化被广泛重塑，将数百个神经元基因从层状转移到斑点，包括在Lys27 （H3K27me3）和Lys4 （H3K4me3）处组蛋白H3三甲基化的关键神经发育基因。在膜层，二价基因的表达异常低，重新定位到斑点可以提高二价染色质对H3K4me3单价的分辨率，并使转录增加8倍以上。

该团队进一步证明，靠近核外周——而不是H3K27me3的存在——维持了嵌入在膜中的二价基因的低表达和平衡状态。该团队发现，层的抑制环境与细胞核外周转录延伸机制的空间隔离有关。他们的结果建立了一种范式，在这种范式中，了解基因的空间位置对于理解其表观基因组调控是必要的。

研究人员表示，核基因组通过大的染色体结构域与亚核室的物理关联在空间上组织成一个三维结构，包括径向外围的核板和核质内的核斑。然而，高阶空间基因组结构如何调节人类发育一直被忽视，染色质状态和亚核基因组区隔化之间的相互作用也知之甚少。

附：英文原文

Title: Subnuclear genome compartmentalization controls bivalent chromatin activity

Author: Ahanger, Sajad Hamid, Semenza, Evan R., Zhang, Chujing, Gil, Eugene, Cole, Mitchel A., Lu, Serena Huei-An, Wang, Li, Kriegstein, Arnold R., Lim, Daniel A.

Issue&Volume: 2026-07-22

Abstract: The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1,2,3,4,5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood. Here we generate high-resolution maps of genomic interactions with the lamina and speckles in cells of the neurogenic lineage isolated from mid-gestational human cortex, identifying an intimate association between subnuclear genome compartmentalization, chromatin state and transcription. During cortical neurogenesis, subnuclear genome compartmentalization is extensively remodelled, relocating hundreds of neuronal genes from the lamina to speckles, including key neurodevelopmental genes bivalent for trimethylation of histone H3 at Lys27 (H3K27me3) and Lys4 (H3K4me3). At the lamina, bivalent genes have exceptionally low expression, and relocation to speckles enhances resolution of bivalent chromatin to H3K4me3 monovalency and increases transcription more than eightfold. We further demonstrate that proximity to the nuclear periphery—not the presence of H3K27me3—maintains the lowly expressed, poised state of bivalent genes embedded in the lamina. We find that the repressive environment of the lamina is associated with spatial segregation of the transcriptional elongation machinery from the nuclear periphery. Our results establish a paradigm in which knowing the spatial location of a gene is necessary for understanding its epigenomic regulation.

DOI: 10.1038/s41586-026-10832-w

Source: https://www.nature.com/articles/s41586-026-10832-w

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com/

投稿链接：http://www.nature.com/authors/submit_manuscript.html