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Lamins organize the global three-dimensional genome from the nuclear periphery

Xiaobin Zheng, Jiabiao Hu, Sibiao Yue, Lidya Kristiani, Miri Kim, Michael Sauria, James Taylor, Youngjo Kim, Yixian Zheng
doi: https://doi.org/10.1101/211656
Xiaobin Zheng
Department of Embryology, Carnegie Institution for Science;
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Jiabiao Hu
Department of Embryology, Carnegie Institution for Science;
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Sibiao Yue
Department of Embryology, Carnegie Institution for Science;
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Lidya Kristiani
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University;
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Miri Kim
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University;
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Michael Sauria
Department of Biology & Department of Computer Science, The Johns Hopkins University
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James Taylor
Department of Biology & Department of Computer Science, The Johns Hopkins University
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Youngjo Kim
Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University;
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Yixian Zheng
Department of Embryology, Carnegie Institution for Science;
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  • For correspondence: zheng@carnegiescience.edu
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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 ES cells. 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 changes of active and inactive chromatin domain interactions. 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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The copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.
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  • Posted October 31, 2017.

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Lamins organize the global three-dimensional genome from the nuclear periphery
Xiaobin Zheng, Jiabiao Hu, Sibiao Yue, Lidya Kristiani, Miri Kim, Michael Sauria, James Taylor, Youngjo Kim, Yixian Zheng
bioRxiv 211656; doi: https://doi.org/10.1101/211656
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Lamins organize the global three-dimensional genome from the nuclear periphery
Xiaobin Zheng, Jiabiao Hu, Sibiao Yue, Lidya Kristiani, Miri Kim, Michael Sauria, James Taylor, Youngjo Kim, Yixian Zheng
bioRxiv 211656; doi: https://doi.org/10.1101/211656

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