Smith Cheryl L, Lan Yemin, Jain Rajan, Epstein Jonathan A, Poleshko Andrey
Department of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Medicine, Penn Cardiovascular Institute, and Institute of Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sci Adv. 2021 Sep 24;7(39):eabj3035. doi: 10.1126/sciadv.abj3035.
The nuclear architecture of rod photoreceptor cells in nocturnal mammals is unlike that of other animal cells. Murine rod cells have an “inverted” chromatin organization with euchromatin at the nuclear periphery and heterochromatin packed in the center of the nucleus. In conventional nuclear architecture, euchromatin is mostly in the interior, and heterochromatin is largely at the nuclear periphery. We demonstrate that inverted nuclear architecture is achieved through global relabeling of the rod cell epigenome. During rod cell maturation, H3K9me2-labeled nuclear peripheral heterochromatin is relabeled with H3K9me3 and repositioned to the nuclear center, while transcriptionally active euchromatin is labeled with H3K9me2 and positioned at the nuclear periphery. Global chromatin relabeling is correlated with spatial rearrangement, suggesting a critical role for histone modifications, specifically H3K9 methylation, in nuclear architecture. These results reveal a dramatic example of genome-wide epigenetic relabeling of chromatin that accompanies altered nuclear architecture in a postnatal, postmitotic cell.
夜行性哺乳动物视杆光感受器细胞的核结构不同于其他动物细胞。小鼠视杆细胞具有“倒置”的染色质组织，常染色质位于核周，异染色质聚集在细胞核中心。在传统的核结构中，常染色质大多位于内部，而异染色质主要位于核周。我们证明，倒置的核结构是通过视杆细胞表观基因组的全局重新标记实现的。在视杆细胞成熟过程中，H3K9me2标记的核周异染色质被H3K9me3重新标记并重新定位到细胞核中心，而转录活跃的常染色质则被H3K9me2标记并定位在核周。全局染色质重新标记与空间重排相关，表明组蛋白修饰，特别是H3K9甲基化，在核结构中起关键作用。这些结果揭示了一个在出生后、有丝分裂后的细胞中，伴随着核结构改变的全基因组染色质表观遗传重新标记的显著例子。
