Skip to main content

Quantitative Analysis of Genome-Wide Chromatin Remodeling

  • Protocol
  • First Online:
Chromatin Remodeling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 833))

Abstract

Recent high-throughput sequencing technologies have opened the door for genome-wide characterization of chromatin features at an unprecedented resolution. Chromatin accessibility is an important property that regulates protein binding and other nuclear processes. Here, we describe computational methods to analyze chromatin accessibility using DNaseI hypersensitivity by sequencing (DNaseI-seq). Although there are numerous bioinformatic tools to analyze ChIP-seq data, our statistical algorithm was developed specifically to identify significantly accessible genomic regions by handling features of DNaseI hypersensitivity. Without prior knowledge of relevant protein factors, one can discover genome-wide chromatin remodeling events associated with specific conditions or differentiation stages from quantitative analysis of DNaseI hypersensitivity. By performing appropriate subsequent computational analyses on a select subset of remodeled sites, it is also possible to extract information about putative factors that may bind to specific DNA elements within DNaseI hypersensitive sites. These approaches enabled by DNaseI-seq represent a powerful new methodology that reveals mechanisms of transcriptional regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wiench, M., Miranda, T. B., and Hager, G. L. (2011) Control of nuclear receptor function by local chromatin structure. FEBS J., 278(13): 2211–30.

    Google Scholar 

  2. John, S., Sabo, P. J., Thurman, R. E., Sung, M. H, Biddie, S. C., Johnson, T. A., Hager, G. L., and Stamatoyannopoulos, J. A. (2011) Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat. Genet., 43, 264–268.

    Google Scholar 

  3. Sabo, P. J., Kuehn, M. S., Thurman, R., Johnson, B. E., Johnson, E., M, Cao, H., Yu, M., Rosenzweig, E., Goldy, J., Haydock, A., Weaver, M., Shafer, A., Lee, K., Neri, F., Humbert, R., Singer, M. A., Richmond, T. A., Dorschner, M. O., McArthur, M., Hawrylycz, M., Green, R. D., Navas, P. A., Noble, W. S., and Stamatoyannopoulos, J. A. (2006) Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nat. Methods, 3, 511–518.

    Google Scholar 

  4. Siersbaek, R., Nielsen, R., John, S., Sung, M. H., Baek, S., Loft, A., Hager, G. L., and Mandrup, S. (2011) Adipogenic development is associated with extensive early remodeling of the chromatin landscape and establishment of transcription factor ‘hotspots’. EMBO J., 30, 1–14.

    Google Scholar 

  5. Hager, G. L., Nagaich, A. K., Johnson, T. A., Walker, D. A., and John, S. (2004) Dynamics of nuclear receptor movement and transcription. Biochim. Biophys. Acta, 1677, 46–51.

    Google Scholar 

  6. Hager, G. L., Elbi, C., Johnson, T. A., Voss, T. C., Nagaich, A. K., Schiltz, R. L., Qiu, Y., and John, S. (2006) Chromatin dynamics and the evolution of alternate promoter states. Chromosome. Res., 14, 107–116.

    Google Scholar 

  7. Hager, G. L. (2009) Footprints by deep sequen-cing. Nat. Methods, 6, 254–255.

    Google Scholar 

  8. Crawford, G. E., Davis, S., Scacheri, P. C., Renaud, G., Halawi, M. J., Erdos, M. R., Green, R., Meltzer, P. S., Wolfsberg, T. G., and Collins, F. S. (2006) DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nat. Methods, 3, 503–509.

    Google Scholar 

  9. Boyle, A. P., Davis, S., Shulha, H. P., Meltzer, P., Margulies, E. H., Weng, Z., Furey, T. S., and Crawford, G. E. (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell, 132, 311–322.

    Google Scholar 

  10. Hesselberth, J. R., Zhang, Z.,, Sabo, P. J., Chen, X., Sandstrom, R., Reynolds, A. P., Thurman, R. E., Neph, S., Kuehn, M. S., Noble, W. S., Fields, S., and Stamatoyannopoulos, J. A. (2009) Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat. Methods, 6, 283–289.

    Google Scholar 

  11. Ling, G., Sugathan, A., Mazor, T., Fraenkel, E., and Waxman, D. J. (2010) Unbiased, genome-wide in vivo mapping of transcriptional regulatory elements reveals sex differences in chromatin structure associated with sex-specific liver gene expression. Mol Cell Biol, 30, 5531–5544.

    Google Scholar 

  12. Bailey, T. L. and Gribskov, M. (1998) Combining evidence using p-values: application to sequence homology searches. Bioinformatics., 14, 48–54.

    Google Scholar 

  13. Bailey, T. L., Williams, N., Misleh, C., and Li, W. W. (2006) MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res., 34, W369–W373.

    Google Scholar 

  14. Bailey, T. L. and Elkan, C. (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc. Int. Conf. Intell. Syst. Mol Biol, 2, 28–36.

    Google Scholar 

  15. Gupta, S., Stamatoyannopoulos, J. A., Bailey, T. L., and Noble, W. S. (2007) Quantifying similarity between motifs. Genome Biol, 8, R24.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gordon L. Hager .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Baek, S., Sung, MH., Hager, G.L. (2012). Quantitative Analysis of Genome-Wide Chromatin Remodeling. In: Morse, R. (eds) Chromatin Remodeling. Methods in Molecular Biology, vol 833. Humana Press. https://doi.org/10.1007/978-1-61779-477-3_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-477-3_26

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-476-6

  • Online ISBN: 978-1-61779-477-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics