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Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA

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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.

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Figure 1: Comparison of ChIP-seq data acquired by Illumina or Helicos sequencing.
Figure 2
Figure 3: Comparison of ChIP-seq data obtained for small-quantity samples.

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  • 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.


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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.

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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.

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Correspondence to Bradley E Bernstein.

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Competing interests

F.O., C.H. and P.M.M. are employees of Helicos BioSciences Corporation.

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Supplementary Figures 1–13 and Supplementary Tables 1–4 (PDF 3579 kb)

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Goren, A., Ozsolak, F., Shoresh, N. et al. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA. Nat Methods 7, 47–49 (2010).

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