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Mol Cell. 2018 Sep 6;71(5):802-815.e7. doi: 10.1016/j.molcel.2018.05.017. Epub 2018 Jun 28.

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

Author information

1
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Electronic address: xzheng@carnegiescience.edu.
2
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
3
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro, Cheonan-si, Chungcheongnam-do 31151, Korea.
4
Department of Biology and Department of Computer Science, The Johns Hopkins University, Baltimore, MD 21218, USA.
5
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro, Cheonan-si, Chungcheongnam-do 31151, Korea. Electronic address: yjokim@sch.ac.kr.
6
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Electronic address: zheng@carnegiescience.edu.

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.

KEYWORDS:

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

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