近日，美国加州大学教授Abigail Buchwalter及其小组的最新研究探明了核外周通过抑制H3k9me2标记的基因和转座子来决定细胞的命运。这一研究成果于2025年7月22日发表在国际顶尖学术期刊《自然—细胞生物学》上。

在本研究中，该研究组在同主题胚胎干细胞中去除三个核层蛋白和层蛋白B受体（LBR），并发现异染色质从核外周分离。突变的同主题胚胎干细胞保持原始多能性，并在整个基因组中维持H3K9me2，但不能抑制H3K9me2标记的基因或转座子。此外，突变细胞不能分化为上皮细胞样细胞，这一转变需要H3K9me2在整个基因组中扩增。突变的表母细胞样细胞可以沉默原始多能性基因并激活表母细胞阶段基因。

然而，H3K9me2不能抑制替代命运的标记，包括原始内胚层。该课题组人员得出结论，膜层和LBR控制着h3k9me2标记的异染色质的空间位置、动态重塑和抑制能力，从而决定细胞的命运。

研究人员表示，在后生动物中，以组蛋白H3赖氨酸9二甲基化（H3K9me2）标记的异染色质位点富集于核外围，但空间位置对异染色质功能的影响尚未明确。

附：英文原文

Title: The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate

Author: Marin, Harold C., Allen, Charlie, Simental, Eric, Martin, Eric W., Panning, Barbara, Al-Sady, Bassem, Buchwalter, Abigail

Issue&Volume: 2025-07-22

Abstract: Heterochromatic loci marked by histone H3 lysine 9 dimethylation (H3K9me2) are enriched at the nuclear periphery in metazoans, but the effect of spatial position on heterochromatin function has not been defined. Here we remove three nuclear lamins and the lamin B receptor (LBR) in mouse embryonic stem cells and show that heterochromatin detaches from the nuclear periphery. Mutant mouse embryonic stem cells sustain naive pluripotency and maintain H3K9me2 across the genome but cannot repress H3K9me2-marked genes or transposons. Further, mutant cells fail to differentiate into epiblast-like cells, a transition that requires the expansion of H3K9me2 across the genome. Mutant epiblast-like cells can silence naive pluripotency genes and activate epiblast-stage genes. However, H3K9me2 cannot repress markers of alternative fates, including primitive endoderm. We conclude that the lamins and LBR control the spatial position, dynamic remodelling and repressive capacity of H3K9me2-marked heterochromatin to shape cell fate decisions.

DOI: 10.1038/s41556-025-01703-z

Source: https://www.nature.com/articles/s41556-025-01703-z