RT Journal Article
SR Electronic
T1 Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 004614
DO 10.1101/004614
A1 Lucas D. Ward
A1 Junbai Wang
A1 Harmen J. Bussemaker
YR 2014
UL http://biorxiv.org/content/early/2014/04/29/004614.abstract
AB 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.ChIPchromatin immunoprecipitationDamIDDNA adenine methyltransferase identificationDBDDNA-binding domainIgGimmunoglobulin GLFElog2 fold enrichmentHOThigh-occupancy targetMLFEmedian log2 fold enrichmentncRNAnoncoding RNAPBMprotein-binding microarrayRPribosomal proteinTFtranscription factorYPDyeast extract peptone dextrose