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

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Item Type:Article
Title:HOT or not: examining the basis of high-occupancy target regions
Creators Name:Wreczycka, K. and Franke, V. and Uyar, B. and Wurmus, R. and Bulut, S. and Tursun, B. and Akalin, A.
Abstract:High-occupancy target (HOT) regions are 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 consequently 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, 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.
Keywords:Amino Acid Motifs, Artifacts, Binding Sites, Caenorhabditis elegans, Chromatin Immunoprecipitation, DNA, DNA Sequence Analysis, Drosophila melanogaster, False Positive Reactions, G-Quadruplexes, Genetic Promoter Regions, Genome, Genomics, Human Genome, Protein Binding, Protein Domains, RNA, Transcription Factors, Animals, Mice
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:gkz460
Date:20 June 2019
Official Publication:https://doi.org/10.1093/nar/gkz460
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/16392/Preprint version

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