DNaseI Seq or DNase-Seq

DNase l Hypersensitive Sites Sequencing

DNase I footprinting was first published in 1978 (Galas et al., 1978) and predates both Sanger sequencing and NGS. The first published use with NGS was published by Boyle et al. 2008 (Boyle et al., 2008) and later optimized for sequencing (Anderson et al., 1981). A high-sensitivity protocol is also available (scDNase-seq) (Jin et al., 2015).

In this method, DNA-protein complexes are treated with DNase l, followed by DNA extraction and sequencing. Sequences bound by regulatory proteins are protected from DNase l digestion. Deep sequencing provides accurate representation of the location of regulatory proteins in the genome. In a variation on this approach, the DNA-protein complexes are stabilized by formaldehyde crosslinking before DNase I digestion. The crosslinking is reversed before DNA purification. In an alternative modification, called GeF-seq, both the crosslinking and the DNase I digestion are carried out in vivo, within permeabilized cells (Chumsakul et al., 2013)

Advantages:

  • Can detect –open” chromatin (Zentner et al., 2012)
  • No prior knowledge of the sequence or binding protein is required
  • Compared to formaldehyde-assisted isolation of regulatory elements and sequencing (FAIRE-seq), has greater sensitivity at promoters (Kumar et al., 2013)

Disadvantages:

  • DNase l is sequence-specific and hypersensitive sites might not account for the entire genome (Yan et al., 2016)
  • DNA loss through the multiple purification steps limits sensitivity (Lu et al., 2016)
  • Integration of DNase I with ChIP data is necessary to identify and differentiate similar protein-binding sites


Reagents:

Illumina Library prep and Array Kit Selector



Reviews:

Chaitankar V., Karakulah G., Ratnapriya R., Giuste F. O., Brooks M. J., et al. Next generation sequencing technology and genomewide data analysis: Perspectives for retinal research. Prog Retin Eye Res. 2016;55:1-31

Yan H., Tian S., Slager S. L., Sun Z. and Ordog T. Genome-Wide Epigenetic Studies in Human Disease: A Primer on -Omic Technologies. Am J Epidemiol. 2016;183:96-109



References:

Qiu Z., Li R., Zhang S., et al. Identification of Regulatory DNA Elements Using Genome-wide Mapping of DNase I Hypersensitive Sites during Tomato Fruit Development. Mol Plant. 2016;9:1168-1182

Frank C. L., Manandhar D., Gordan R. and Crawford G. E. HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells. Epigenetics Chromatin. 2016;9:15

Lu F., Liu Y., Inoue A., Suzuki T., Zhao K., et al. Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development. Cell. 2016;165:1375-1388

Badal S. S., Wang Y., Long J., et al. miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy. Nat Commun. 2016;7:12076

Adar S., Hu J., Lieb J. D. and Sancar A. Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis. Proc Natl Acad Sci U S A. 2016;113:E2124-2133

Bevington S. L., Cauchy P., Piper J., Bertrand E., Lalli N., et al. Inducible chromatin priming is associated with the establishment of immunological memory in T cells. EMBO J. 2016;35:515-535

Browne J. A., Yang R., Eggener S. E., Leir S. H. and Harris A. HNF1 regulates critical processes in the human epididymis epithelium. Mol Cell Endocrinol. 2016;425:94-102

Chaitankar V., Karakulah G., Ratnapriya R., Giuste F. O., Brooks M. J., et al. Next generation sequencing technology and genomewide data analysis: Perspectives for retinal research. Prog Retin Eye Res. 2016;55:1-31

Corces M. R., Buenrostro J. D., Wu B., Greenside P. G., Chan S. M., et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat Genet. 2016;48:1193-1203

Georgakilas G., Vlachos I. S., Zagganas K., et al. DIANA-miRGen v3.0: accurate characterization of microRNA promoters and their regulators. Nucleic Acids Res. 2016;44:D190-195

Lensing S. V., Marsico G., Hansel-Hertsch R., Lam E. Y., Tannahill D. and Balasubramanian S. DSBCapture: in situ capture and sequencing of DNA breaks. Nat Methods. 2016;13:855-857

Metser G., Shin H. Y., Wang C., et al. An autoregulatory enhancer controls mammary-specific STAT5 functions. Nucleic Acids Res. 2016;44:1052-1063

Schmidt S. F., Madsen J. G., Frafjord K. O., Poulsen L., Salo S., et al. Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORgamma Axis Regulating Proliferation in beta Cells. Cell Rep. 2016;16:2359-2372

Shin H. Y., Willi M., Yoo K. H., et al. Hierarchy within the mammary STAT5-driven Wap super-enhancer. Nat Genet. 2016;48:904-911

Thompson B., Varticovski L., Baek S. and Hager G. L. Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation. PLoS One. 2016;11:e0148619

Yang R., Kerschner J. L., Gosalia N., et al. Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus. Nucleic Acids Res. 2016;44:3082-3094