I hope that some of you may have a recommendation regarding the use of paired-end sequencing over single-end for ChIP-seq. In principle we expect only a minor improvement of using paired-end sequencing for ChIP-seq analysis over single-end. Since paired-end sequencing is more expensive and the processing of the data takes longer time we will like to confidently decide when is worth to use paired-end and when is not.
In the past, we noticed that in the case of ChIPs targeting long repetitive regions the use of paired-end sequencing helped significantly to identify enrichments where single reads will not map uniquely. Off course we only got enrichments at the flanks of the repetitive regions.
We are about to run some tests to compare paired-end vs. single-end for more 'standard' cases but it never hurts to address the collective knowledge for advice.