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Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast

View ORCID ProfileLucas D. Ward, Junbai Wang, Harmen J. Bussemaker
doi: https://doi.org/10.1101/004614
Lucas D. Ward
1Department of Biological Sciences, Columbia University, 1212 Amsterdam Ave., New York, NY 10027, USA
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  • ORCID record for Lucas D. Ward
Junbai Wang
1Department of Biological Sciences, Columbia University, 1212 Amsterdam Ave., New York, NY 10027, USA
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Harmen J. Bussemaker
1Department of Biological Sciences, Columbia University, 1212 Amsterdam Ave., New York, NY 10027, USA
2Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave., New York, NY 10032, USA
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  • For correspondence: lukeward@mit.edu junbai.wang@rr-research.no hjb2004@columbia.edu
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ABSTRACT

Background Recent chromatin immunoprecipitation (ChIP) experiments in fly, mouse, and human have revealed the existence of high-occupancy target (HOT) regions or “hotspots” that show enrichment across many assayed DNA-binding proteins. Similar co-enrichment observed in yeast so far has been treated as artifactual, and has not been fully characterized.

Results Here we reanalyze ChIP data from both array-based and sequencing-based experiments to show that in the yeast S. cerevisiae, the collective enrichment phenomenon is strongly associated with proximity to noncoding RNA genes and with nucleosome depletion. DNA sequence motifs that confer binding affinity for the proteins are largely absent from these hotspots, suggesting that protein-protein interactions play a prominent role. The hotspots are condition-specific, suggesting that they reflect a chromatin state or protein state, and are not a static feature of underlying sequence. Additionally, only a subset of all assayed factors is associated with these loci, suggesting that the co-enrichment cannot be simply explained by a chromatin state that is universally more prone to immunoprecipitation.

Conclusions Together our results suggest that the co-enrichment patterns observed in yeast represent transcription factor co-occupancy. More generally, they make clear that great caution must be used when interpreting ChIP enrichment profiles for individual factors in isolation, as they will include factor-specific as well as collective contributions.

  • ABBREVIATIONS

    ChIP
    chromatin immunoprecipitation
    DamID
    DNA adenine methyltransferase identification
    DBD
    DNA-binding domain
    IgG
    immunoglobulin G
    LFE
    log2 fold enrichment
    HOT
    high-occupancy target
    MLFE
    median log2 fold enrichment
    ncRNA
    noncoding RNA
    PBM
    protein-binding microarray
    RP
    ribosomal protein
    TF
    transcription factor
    YPD
    yeast extract peptone dextrose
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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    Posted April 29, 2014.
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    Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
    Lucas D. Ward, Junbai Wang, Harmen J. Bussemaker
    bioRxiv 004614; doi: https://doi.org/10.1101/004614
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    Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
    Lucas D. Ward, Junbai Wang, Harmen J. Bussemaker
    bioRxiv 004614; doi: https://doi.org/10.1101/004614

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