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Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome

Abstract

We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution. Using long crosslinkers and isolation of insoluble chromatin, Micro-C XL increases signal-to-noise ratio. Micro-C XL maps of budding and fission yeast genomes capture both short-range chromosome fiber features such as chromosomally interacting domains and higher order features such as centromere clustering. Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.

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Figure 1: Overview of Micro-C XL.
Figure 2: Analysis of chromosome folding in S. pombe.
Figure 3: Comparison of chromosome folding between S. cerevisiae and S. pombe.

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Acknowledgements

We thank L. Mirny and members of the Rando lab for insightful discussions. Work was supported in part by NIH grant GM079205 to O.J.R. G.F. and A.G. were supported by 4D Nucleome Program grants R01 GM114190 and U54 DK107980. T.-H.S.H. is an HHMI international student research fellow.

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T.-H.S.H. and O.J.R. conceived the study. T.-H.S.H. performed all experiments. G.F. and T.-H.S.H. analyzed data. T.-H.S.H., G.F., A.G., and O.J.R. wrote the manuscript.

Corresponding author

Correspondence to Oliver J Rando.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–18 and Supplementary Protocol (PDF 10017 kb)

Supplementary Data

Read numbers and interactions vs. distance for all datasets. (XLSX 813 kb)

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Hsieh, TH., Fudenberg, G., Goloborodko, A. et al. Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome. Nat Methods 13, 1009–1011 (2016). https://doi.org/10.1038/nmeth.4025

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