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HOT or not: examining the basis of high-occupancy target regions

Katarzyna Wreczycka, Vedran Franke, Bora Uyar, Ricardo Wurmus, View ORCID ProfileAltuna Akalin
doi: https://doi.org/10.1101/107680
Katarzyna Wreczycka
1Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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Vedran Franke
1Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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Bora Uyar
1Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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Ricardo Wurmus
1Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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Altuna Akalin
1Bioinformatics Platform, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
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  • ORCID record for Altuna Akalin
  • For correspondence: altuna.akalin@mdc-berlin.de
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Abstract

High-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 31, 2017.
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HOT or not: examining the basis of high-occupancy target regions
Katarzyna Wreczycka, Vedran Franke, Bora Uyar, Ricardo Wurmus, Altuna Akalin
bioRxiv 107680; doi: https://doi.org/10.1101/107680
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HOT or not: examining the basis of high-occupancy target regions
Katarzyna Wreczycka, Vedran Franke, Bora Uyar, Ricardo Wurmus, Altuna Akalin
bioRxiv 107680; doi: https://doi.org/10.1101/107680

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