Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Biological Science, Florida State University, Tallahassee, FL, USA.
EMBO J. 2020 Mar 16;39(6):e103159. doi: 10.15252/embj.2019103159. Epub 2020 Feb 21.
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.
转录失活的基因通常位于核层（NL），作为大核层相关结构域（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。这个过程是如何进行的，以及它如何影响侧翼染色体区域，目前还知之甚少。我们通过系统地激活或失活单个基因，并对 NL 相互作用、复制时间和转录模式进行详细的全基因组分析，来解决这些问题。LAD 内基因的激活通常会导致整个转录单位与 NL 的分离，但即使多个相邻基因被激活，也很少有超过 50-100kb 的侧翼 DNA 分离。分离的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到早期复制时间的转变相吻合，但后者可能涉及更长的 DNA 片段。活性基因的失活会导致 NL 接触的增加。这些广泛的数据集是通过转录分析 LAD 重排的资源，并揭示了有丝分裂染色体的惊人灵活性。
