Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
1 Department of Biological Sciences, Columbia University, 1212 Amsterdam Ave, New York, NY 10027, USA
2 Center for Computational Biology and Bioinformatics, Columbia University, 1130 St. Nicholas Ave, New York, NY 10032, USA
3 Current address: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
4 Current address: Department of Pathology, Oslo University Hospital - The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
BMC Genomics 2014, 15:494 doi:10.1186/1471-2164-15-494Published: 19 June 2014
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.
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.
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.