Single-end sequencing instead of paired-end sequencing is possible. However, it has drawbacks compared to paired-end sequencing: (i) For abundant targets like histone marks or transcription factors a large number of binding sites is expected. Paired-end sequencing facilitates unambiguous mapping to the correct genomic position. This additional information reduces the necessary sequencing depth. (ii) MNase will digest the target DNA until the section covered by the protein of interest. Paired-end sequencing will reveal this footprint while the information is lost in single-end sequencing.