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Local rewiring of genome-nuclear lamina interactions by transcription.
The EMBO Journal ( IF 11.4 ) Pub Date : 2020-02-21 , DOI: 10.15252/embj.2019103159
Laura Brueckner 1 , Peiyao A Zhao 2 , Tom van Schaik 1 , Christ Leemans 1 , Jiao Sima 2 , Daniel Peric-Hupkes 1 , David M Gilbert 2 , Bas van Steensel 1, 3
Affiliation  

Transcriptionally inactive genes are often positioned at the nuclear lamina (NL), as part of large lamina-associated domains (LADs). Activation of such genes is often accompanied by repositioning toward the nuclear interior. How this process works and how it impacts flanking chromosomal regions are poorly understood. We addressed these questions by systematic activation or inactivation of individual genes, followed by detailed genome-wide analysis of NL interactions, replication timing, and transcription patterns. Gene activation inside LADs typically causes NL detachment of the entire transcription unit, but rarely more than 50-100 kb of flanking DNA, even when multiple neighboring genes are activated. The degree of detachment depends on the expression level and the length of the activated gene. Loss of NL interactions coincides with a switch from late to early replication timing, but the latter can involve longer stretches of DNA. Inactivation of active genes can lead to increased NL contacts. These extensive datasets are a resource for the analysis of LAD rewiring by transcription and reveal a remarkable flexibility of interphase chromosomes.

中文翻译:

通过转录局部重新连接基因组-核叶片相互作用。

转录无活性基因通常位于核层(NL),作为大的层相关域(LAD)的一部分。此类基因的激活通常伴随着向核内部的重新定位。对该过程如何工作以及如何影响侧翼染色体区域了解得很少。我们通过单个基因的系统激活或失活,接着是NL相互作用,复制时间和转录模式的详细全基因组分析,解决了这些问题。LAD内部的基因激活通常会导致整个转录单元的NL分离,但即使激活了多个相邻基因,也很少超过50-100 kb的侧翼DNA。分离程度取决于表达水平和激活基因的长度。NL相互作用的丧失与从晚期复制到早期复制的时机相吻合,但是后者可能需要更长的DNA延伸时间。活性基因的失活可以导致NL接触增加。这些广泛的数据集可用于通过转录分析LAD的重新布线,并揭示相间染色体的显着灵活性。
更新日期:2020-03-19
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