PT  - JOURNAL ARTICLE
AU  - Xiaobin Zheng
AU  - Jiabiao Hu
AU  - Sibiao Yue
AU  - Lidya Kristiani
AU  - Miri Kim
AU  - Michael Sauria
AU  - James Taylor
AU  - Youngjo Kim
AU  - Yixian Zheng
TI  - Lamins organize the global three-dimensional genome from the nuclear periphery
AID  - 10.1101/211656
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 211656
4099  - http://biorxiv.org/content/early/2017/10/31/211656.short
4100  - http://biorxiv.org/content/early/2017/10/31/211656.full
AB  - 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.HighlightsLamin loss does not affect the overall TAD structure but alters TAD-TAD interactionsLamin null ES cells exhibit decondensation or detachment of specific LAD regionsExpansion and detachment of LADs can alter genome-wide 3D chromatin interactionsAltered chromatin domain interactions are correlated with altered transcription