Molecular Cell
Volume 71, Issue 5, 6 September 2018, Pages 802-815.e7
Journal home page for Molecular Cell

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

https://doi.org/10.1016/j.molcel.2018.05.017Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Lamin loss does not affect the overall TAD structure but alters TAD-TAD interactions

  • Lamin null ESCs exhibit decondensation or detachment of specific LAD regions

  • Expansion and detachment of LADs can alter genome-wide 3D chromatin interactions

  • Altered chromatin domain interactions are correlated with altered transcription

Summary

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.

Keywords

lamin
nuclear lamina
3D genome
TADs
histone and lamina landscape
HiLands
Hi-C
transcription
lamina-associated chromatin domains
LADs

Cited by (0)

4

These authors contributed equally

5

Lead Contact