Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery

Molecular Cell
Xiaobin ZhengYixian Zheng

Abstract

Lamins are structural components of the nuclear lamina (NL) that regulate genome organization and gene expression, but the mechanism remains unclear. Using Hi-C, we show that lamins maintain proper interactions among the topologically associated chromatin domains (TADs) but not their overall architecture. Combining Hi-C with fluorescence in situ hybridization (FISH) and analyses of lamina-associated domains (LADs), we reveal that lamin loss causes expansion or detachment of specific LADs in mouse ESCs. The detached LADs disrupt 3D interactions of both LADs and interior chromatin. 4C and epigenome analyses further demonstrate that lamins maintain the active and repressive chromatin domains among different TADs. By combining these studies with transcriptome analyses, we found a significant correlation between transcription changes and the interaction changes of active and inactive chromatin domains These findings provide a foundation to further study how the nuclear periphery impacts genome organization and transcription in development and NL-associated diseases.

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Related Concepts

Lamins
Study
Hic1
Fluorescent in Situ Hybridization
Genome
Three-dimensional
Nuclear Lamina
Associative Aphasia
Blade - plant part
Transcription, Genetic

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