Abstract
Chromatin structure and transcription factor localization can be assayed genome-wide by sequencing genomic DNA fractionated by protein occupancy or other properties, but current technologies involve multiple steps that introduce bias and inefficiency. Here we apply a single-molecule approach to directly sequence chromatin immunoprecipitated DNA with minimal sample manipulation. This method is compatible with just 50 pg of DNA and should thus facilitate charting chromatin maps from limited cell populations.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Change history
12 April 2010
In the version of this supplementary file originally posted online, Figure 1 was truncated. The error has been corrected in this file as of 12 April 2010.
References
Barski, A. et al. Cell 129, 823–837 (2007).
Johnson, D.S. et al. Science 316, 1497–1502 (2007).
Mikkelsen, T.S. et al. Nature 448, 553–560 (2007).
Robertson, G. et al. Nat. Methods 4, 651–657 (2007).
Boyle, A.P. et al. Cell 132, 311–322 (2008).
Hesselberth, J.R. et al. Nat. Methods 6, 283–289 (2009).
Down, T.A. et al. Nat. Biotechnol. 26, 779–785 (2008).
Harris, T.D. et al. Science 320, 106–109 (2008).
Pushkarev, D., Neff, N.F. & Quake, S.R. Nat. Biotechnol. 27, 847–852 (2009).
Kim, T.H. et al. Cell 128, 1231–1245 (2007).
Dohm, J.C. et al. Nucleic Acids Res. 36, e105 (2008).
Tolstorukov, M.Y. et al. Genome Res. 19, 967–977 (2009).
Kozarewa, I. et al. Nat. Methods 6, 291–295 (2009).
Bowers, J. et al. Nat. Methods 6, 593–595 (2009).
Lipson, D. et al. Nat. Biotechnol. 27, 652–658 (2009).
Batzoglou, S. et al. Genome Res. 12, 177–189 (2002).
Acknowledgements
We thank J. Robinson and members of the IGV platform for their help with data presentation. A.G. is supported by an EMBO long-term postdoctoral fellowship. M.K. is supported by a Croucher Foundation fellowship. A.R. is an investigator of the Merkin Foundation for Stem Cell Research at the Broad Institute. This research was supported by funds from the Burroughs Wellcome Fund (to B.E.B. and A.R.), Howard Hughes Medical Institute (to B.E.B. and A.R.), Partnership for Cures Culpeper Scholarship (to B.E.B.) and the US National Human Genome Research Institute.
Author information
Authors and Affiliations
Contributions
A.G., N.S. and B.E.B. processed and analyzed the data, wrote the paper and made the figures; F.O., C.H. and P.M.M. developed the method for sequencing ChIP-DNA and performed the sequencing; M.K. performed the chromatin experiments; M.A., M.G., O.Z. and A.R. helped with data analysis.
Corresponding author
Ethics declarations
Competing interests
F.O., C.H. and P.M.M. are employees of Helicos BioSciences Corporation.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–13 and Supplementary Tables 1–4 (PDF 3579 kb)
Rights and permissions
About this article
Cite this article
Goren, A., Ozsolak, F., Shoresh, N. et al. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA. Nat Methods 7, 47–49 (2010). https://doi.org/10.1038/nmeth.1404
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmeth.1404
This article is cited by
-
ZFP281-BRCA2 prevents R-loop accumulation during DNA replication
Nature Communications (2022)
-
Development of a sequencing system for spatial decoding of DNA barcode molecules at single-molecule resolution
Communications Biology (2020)
-
Solid-phase enzyme catalysis of DNA end repair and 3′ A-tailing reduces GC-bias in next-generation sequencing of human genomic DNA
Scientific Reports (2018)
-
A microfluidic device for epigenomic profiling using 100 cells
Nature Methods (2015)
-
Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells
Genome Biology (2013)