Inferring Protein-DNA Binding Profiles at Interspersed Repeats Using HiChIP and PAtChER

Alignment of short-read sequencing data to interspersed genomic repeats, such as transposable elements, can be problematic. This is especially true for evolutionarily young elements, which have not sufficiently diverged from each other to produce distinct and uniquely mappable reads. Mapping difficulties pose a challenge for studying the portfolio of epigenetic modifications and other chromatin regulators that bind to transposons and dictate their activity, which are typically studied using chromatin immunoprecipitation followed by sequencing (ChIP-seq). Since ChIP-seq requires chromatin fragmentation to achieve appropriate resolution, longer reads do not appreciably improve mappability. Here, we present an experimental and computational protocol that couples ChIP-seq with 3D genome folding information to produce protein binding profiles with dramatically increased coverage at interspersed repeats.