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HiChIP: efficient and sensitive analysis of protein-directed genome architecture

Nature Methods volume 13, pages 919922 (2016) | Download Citation

Abstract

Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.

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Acknowledgements

We thank our lab members for discussion. We thank N. Suliman for her critical reading of the manuscript. This work was supported by the Stanford Genome Training Program (NIH/NHGRI) (M.R.M.); Human Frontier Science Program, Rita Allen Foundation, Bio-X Stanford Interdisciplinary Graduate Fellowship (A.J.R.); National Institutes of Health (NIH) 1F30CA189514-01 Stanford Medical Scientist Program (R.A.F.); NIH U19AI057266 (to W.J.G.) and P50-HG007735 (to. H.Y.C. and W.J.G.); and NIH S10OD018220 to Stanford Functional Genomics Facility.

Author information

Author notes

    • Maxwell R Mumbach
    • , Adam J Rubin
    •  & Ryan A Flynn

    These authors contributed equally to this work.

Affiliations

  1. Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.

    • Maxwell R Mumbach
    • , Ryan A Flynn
    • , Chao Dai
    • , William J Greenleaf
    •  & Howard Y Chang
  2. Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.

    • Maxwell R Mumbach
    • , Adam J Rubin
    • , Ryan A Flynn
    • , Chao Dai
    • , Paul A Khavari
    •  & Howard Y Chang
  3. Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

    • Maxwell R Mumbach
    •  & William J Greenleaf
  4. Department of Applied Physics, Stanford University, Stanford, California, USA.

    • William J Greenleaf

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Contributions

M.R.M. and R.A.F. developed the method. M.R.M. performed experiments. A.J.R. and C.D. analyzed the data. M.R.M., A.J.R., R.A.F., C.D., P.A.K., W.J.G., and H.Y.C. interpreted the results and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Howard Y Chang.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–9 and Supplementary Protocol

Excel files

  1. 1.

    Supplementary Table 1

    Comparison of sequencing and experimental statistics between recently published ChIA-PET and Capture-C data with HiChIP.

  2. 2.

    Supplementary Table 2

    Detailed sequencing and experimental statistics for HiChIP.

  3. 3.

    Supplementary Table 3

    High confidence Juicer loop calls from GM12878 Smc1a,mESC Smc1a, and mESC Oct4 HiChIP experiments.

  4. 4.

    Supplementary Table 4

    PCR primer sequences and barcodes used in HiChIP experiments.

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DOI

https://doi.org/10.1038/nmeth.3999