Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.

Accession codes

Primary accessions

Gene Expression Omnibus


  1. 1

    Dekker, J., Marti-Renom, M.A. & Mirny, L.A. Nat. Rev. Genet. 14, 390–403 (2013).

    CAS  Article  Google Scholar 

  2. 2

    Dekker, J. & Misteli, T. Cold Spring Harb. Perspect. Biol. 7, a019356 (2015).

    Article  Google Scholar 

  3. 3

    Horn, P.J. & Peterson, C.L. Science 297, 1824–1827 (2002).

    CAS  Article  Google Scholar 

  4. 4

    Friedman, N. & Rando, O.J. Genome Res. 25, 1482–1490 (2015).

    CAS  Article  Google Scholar 

  5. 5

    Dekker, J., Rippe, K., Dekker, M. & Kleckner, N. Science 295, 1306–1311 (2002).

    CAS  Article  Google Scholar 

  6. 6

    Lieberman-Aiden, E. et al. Science 326, 289–293 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Denker, A. & de Laat, W. Genes Dev. 30, 1357–1382 (2016).

    CAS  Article  Google Scholar 

  8. 8

    Lajoie, B.R., Dekker, J. & Kaplan, N. Methods 72, 65–75 (2015).

    CAS  Article  Google Scholar 

  9. 9

    Hsieh, T.H. et al. Cell 162, 108–119 (2015).

    CAS  Article  Google Scholar 

  10. 10

    Duan, Z. et al. Nature 465, 363–367 (2010).

    CAS  Article  Google Scholar 

  11. 11

    Scherrer, R., Louden, L. & Gerhardt, P. J. Bacteriol. 118, 534–540 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Marbouty, M. et al. eLife 3, e03318 (2014).

    Article  Google Scholar 

  13. 13

    Mizuguchi, T. et al. Nature 516, 432–435 (2014).

    CAS  Article  Google Scholar 

  14. 14

    Henikoff, S., Henikoff, J.G., Sakai, A., Loeb, G.B. & Ahmad, K. Genome Res. 19, 460–469 (2009).

    CAS  Article  Google Scholar 

  15. 15

    Nagano, T. et al. Genome Biol. 16, 175 (2015).

    Article  Google Scholar 

  16. 16

    Gavrilov, A.A. et al. Nucleic Acids Res. 41, 3563–3575 (2013).

    CAS  Article  Google Scholar 

  17. 17

    Rao, S.S. et al. Cell 159, 1665–1680 (2014).

    CAS  Article  Google Scholar 

  18. 18

    Ansari, A. & Hampsey, M. Genes Dev. 19, 2969–2978 (2005).

    CAS  Article  Google Scholar 

  19. 19

    O'Sullivan, J.M. et al. Nat. Genet. 36, 1014–1018 (2004).

    CAS  Article  Google Scholar 

  20. 20

    Lee, K., Hsiung, C.C., Huang, P., Raj, A. & Blobel, G.A. Genes Dev. 29, 1992–1997 (2015).

    CAS  Article  Google Scholar 

  21. 21

    Tsankov, A.M., Thompson, D.A., Socha, A., Regev, A. & Rando, O.J. PLoS Biol. 8, e1000414 (2010).

    Article  Google Scholar 

  22. 22

    Yuan, G.-C. et al. Science 309, 626–630 (2005).

    CAS  Article  Google Scholar 

  23. 23

    Rando, O., Hsieh, T.-H., Fundenberg, G. & Goloborodko, A. Protocol Exchange (2016).

  24. 24

    Imakaev, M. et al. Nat. Methods 9, 999–1003 (2012).

    CAS  Article  Google Scholar 

  25. 25

    Naumova, N. et al. Science 342, 948–953 (2013).

    CAS  Article  Google Scholar 

  26. 26

    Imakaev, M.V., Fudenberg, G. & Mirny, L.A. FEBS Lett. 589, 3031–3036 (2015).

    CAS  Article  Google Scholar 

Download references


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.

Author information




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.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing