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bioRxiv · 10.1101/307892

TSA-Seq Mapping of Nuclear Genome Organization

Chen, Y.·Zhang, Y.·Wang, Y.·Zhang, L.·Brinkman, E. K.·Adam, S. A.·Goldman, R.·van Steensel, B.·Ma, J.·Belmont, A. S.
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Abstract

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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Chen, Y., Zhang, Y., Wang, Y., Zhang, L., Brinkman, E. K., Adam, S. A., Goldman, R., van Steensel, B., Ma, J., Belmont, A. S.. 2018-04-25. TSA-Seq Mapping of Nuclear Genome Organization. https://doi.org/10.1101/307892

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