High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq

Accurate identification of the DNA-binding sites of transcription factors and other DNA-binding proteins on the genome is crucial to understanding their molecular interactions with DNA. Here, we describe a new method: Genome Footprinting by high-throughput sequencing (GeF-seq), which combines in viv...

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Main Authors: Chumsakul, Onuma, Nakamura, Kensuke, Kurata, Tetsuya, Hobman, Jon L., Ogasawara, Naotake, Oshima, Taku, Ishikawa, Shu
Format: Article
Published: Oxford University Press 2013
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Online Access:https://eprints.nottingham.ac.uk/31617/
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author Chumsakul, Onuma
Nakamura, Kensuke
Kurata, Tetsuya
Hobman, Jon L.
Ogasawara, Naotake
Oshima, Taku
Ishikawa, Shu
author_facet Chumsakul, Onuma
Nakamura, Kensuke
Kurata, Tetsuya
Hobman, Jon L.
Ogasawara, Naotake
Oshima, Taku
Ishikawa, Shu
author_sort Chumsakul, Onuma
building Nottingham Research Data Repository
collection Online Access
description Accurate identification of the DNA-binding sites of transcription factors and other DNA-binding proteins on the genome is crucial to understanding their molecular interactions with DNA. Here, we describe a new method: Genome Footprinting by high-throughput sequencing (GeF-seq), which combines in vivo DNase I digestion of genomic DNA with ChIP coupled with high-throughput sequencing. We have determined the in vivo binding sites of a Bacillus subtilis global regulator, AbrB, using GeF-seq. This method shows that exact DNA-binding sequences, which were protected from in vivo DNase I digestion, were resolved at a comparable resolution to that achieved by in vitro DNase I footprinting, and this was simply attained without the necessity of prediction by peak-calling programs. Moreover, DNase I digestion of the bacterial nucleoid resolved the closely positioned AbrB-binding sites, which had previously appeared as one peak in ChAP-chip and ChAP-seq experiments. The high-resolution determination of AbrB-binding sites using GeF-seq enabled us to identify bipartite TGGNA motifs in 96% of the AbrB-binding sites. Interestingly, in a thousand binding sites with very low-binding intensities, single TGGNA motifs were also identified. Thus, GeF-seq is a powerful method to elucidate the molecular mechanism of target protein binding to its cognate DNA sequences.
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spelling nottingham-316172020-05-04T16:36:28Z https://eprints.nottingham.ac.uk/31617/ High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq Chumsakul, Onuma Nakamura, Kensuke Kurata, Tetsuya Hobman, Jon L. Ogasawara, Naotake Oshima, Taku Ishikawa, Shu Accurate identification of the DNA-binding sites of transcription factors and other DNA-binding proteins on the genome is crucial to understanding their molecular interactions with DNA. Here, we describe a new method: Genome Footprinting by high-throughput sequencing (GeF-seq), which combines in vivo DNase I digestion of genomic DNA with ChIP coupled with high-throughput sequencing. We have determined the in vivo binding sites of a Bacillus subtilis global regulator, AbrB, using GeF-seq. This method shows that exact DNA-binding sequences, which were protected from in vivo DNase I digestion, were resolved at a comparable resolution to that achieved by in vitro DNase I footprinting, and this was simply attained without the necessity of prediction by peak-calling programs. Moreover, DNase I digestion of the bacterial nucleoid resolved the closely positioned AbrB-binding sites, which had previously appeared as one peak in ChAP-chip and ChAP-seq experiments. The high-resolution determination of AbrB-binding sites using GeF-seq enabled us to identify bipartite TGGNA motifs in 96% of the AbrB-binding sites. Interestingly, in a thousand binding sites with very low-binding intensities, single TGGNA motifs were also identified. Thus, GeF-seq is a powerful method to elucidate the molecular mechanism of target protein binding to its cognate DNA sequences. Oxford University Press 2013-04-11 Article PeerReviewed Chumsakul, Onuma, Nakamura, Kensuke, Kurata, Tetsuya, Hobman, Jon L., Ogasawara, Naotake, Oshima, Taku and Ishikawa, Shu (2013) High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq. DNA Research, 20 (4). pp. 325-338. ISSN 1756-1663 GeF-seq; ChIP-seq; AbrB; Bacillus subtilis http://dnaresearch.oxfordjournals.org/content/20/4/325 doi:10.1093/dnares/dst013 doi:10.1093/dnares/dst013
spellingShingle GeF-seq; ChIP-seq; AbrB; Bacillus subtilis
Chumsakul, Onuma
Nakamura, Kensuke
Kurata, Tetsuya
Hobman, Jon L.
Ogasawara, Naotake
Oshima, Taku
Ishikawa, Shu
High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title_full High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title_fullStr High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title_full_unstemmed High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title_short High-resolution mapping of in vivo genomic transcription factor binding sites using in situ DNase I footprinting and ChIP-seq
title_sort high-resolution mapping of in vivo genomic transcription factor binding sites using in situ dnase i footprinting and chip-seq
topic GeF-seq; ChIP-seq; AbrB; Bacillus subtilis
url https://eprints.nottingham.ac.uk/31617/
https://eprints.nottingham.ac.uk/31617/
https://eprints.nottingham.ac.uk/31617/