@article{9c6fa2efe94f458c89c927a4504b49cd,
title = "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler",
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. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells 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, housekeeping 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 spatial organization of transcription and gene expression.",
author = "Yu Chen and Yang Zhang and Yuchuan Wang and Liguo Zhang and Brinkman, {Eva K.} and Adam, {Stephen A.} and Robert Goldman and {Van Steensel}, Bas and Jian Ma and Belmont, {Andrew S.}",
note = "Funding Information: This work was supported by National Institutes of Health grant R01 GM58460 to A.S. Belmont, R01 HG007352 to J. Ma, and U54 DK107965 to A.S. Belmont, J. Ma, and B. van Steensel as well as a Netherlands Organization for Scientific Research ZonMW-TOP grant to B. van Steensel. The authors declare no competing financial interests. Funding Information: This work was supported by National Institutes of Health grant R01 GM58460 to A.S. Belmont, R01 HG007352 to J. Ma, and U54 DK107965 to A.S. Belmont, J. Ma, and B. van Steensel as well as a Netherlands Organization for Scientific Research ZonMW-TOP grant to B. van Steensel. Publisher Copyright: {\textcopyright} 2018 Chen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).",
year = "2018",
month = nov,
day = "1",
doi = "10.1083/jcb.201807108",
language = "English (US)",
volume = "217",
pages = "4025--4048",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "11",
}