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TSA-Seq Mapping of Nuclear Genome Organization

By Yu Chen, Yang Zhang, Yuchuan Wang, Liguo Zhang, Eva K. Brinkman, Stephen A. Adam, Robert Goldman, Bas van Steensel, Jian Ma, Andrew S. Belmont

Posted 25 Apr 2018
bioRxiv DOI: 10.1101/307892 (published DOI: 10.1083/jcb.201807108)

While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. Here we describe TSA-Seq, a new mapping method able to estimate mean chromosomal distances from nuclear speckles genome-wide and predict several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple, spatially separated nuclear domains, including two types of transcription "hot-zones". Transcription hot-zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, house-keeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for nuclear spatial organization of transcription.

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