ChIP-seq reads are notoriously difficult to assign to individual transposon copies. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements, which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Understanding of how individual copies are transcriptionally regulated cannot be appreciated without this information. To overcome this, I propose to leverage chromatin conformation information from Hi-ChIP data, a technique which combines Hi-C with ChIP-seq. As proximal (<50kb) chromatin interactions predominate, mappable genomic fragments are more likely to interact with repeats nearby than those lying far away. To implement this mapping strategy, we have developed PAtChER (Proximity-based alignment of Hi-ChIP ends to repeats). PAtChER employs information from Hi-ChIP chimeric reads to assign the multi-mapping read to a single location in the genome with high accuracy. Importantly, I demonstrate that PAtChER yields accurate protein enrichment profiles at individual repetitive loci. I then applied this to discover previously unappreciated protein positional information at individual transposable elements. This strategy will enable substantial improvements to our current understanding of transposon transcriptional regulation in health and disease and provide an invaluable tool to the transposon field
