This study aimed to make a judgment about how comparable these two methods are – at first glance not very highly – as CUT&Tag only captures just over half of the same data points. But we were reassured as it does capture the most significant and strongest peaks, and shows very similar enrichments in regulatory elements, functional annotations and transcription factor binding sites. We hope that this work will provide useful guidelines for anyone working in the field, particularly those interested in profiling histone modifications, in carrying out future epigenetic research.”
Dr Sarah Marzi, Senior Lecturer at UK DRI at King's
27 March 2025
Guidelines on CUT&Tag to study gene regulation
New study compares CUT&Tag to the existing standard of CHIP-seq, serving as guidelines for studying histone modification.
A new study, published today in Nature Communications, offers a new set of guidelines for designing epigenetic studies. The study is the first to systematically compare the two most widely used techniques to analyse a type of gene regulation mechanism called histone modifications. The guidelines are based on the new technique, CUT&Tag, which captures the most significant and strongest signals in the data when compared to ChIP-seq.
Scientists have continually been developing better ways to study gene regulation – the process through which the expression of genes is controlled by cells. Traditionally, researchers have used the ChIP-seq method to profile histone modifications. However, a newer technique called CUT&Tag has been gaining popularity for being cheaper, more sensitive, and working well with single cells.
To date, there has been no comprehensive study on how best to undertake CUT&Tag experiments and analyse the resulting data. In this study, led by Dr Sarah Marzi, Senior Lecturer in Neuroscience at the UK DRI at King’s, the researchers aimed to benchmark CUT&Tag against the standard method (ChIP-seq).
Dr Marzi and her team assessed CUT&Tag reliability by comparing it to ChIP-seq using data from a well-known human genome database called ENCODE. They checked how much overlap there was, how well their signals matched, and whether they identified the same important regions of DNA related to gene regulation and protein binding.
They found that CUT&Tag detected just over half of the same DNA-protein interaction sides identified by ChIP-seq. While the two approaches are not identical, the new technique of CUT&Tag captures the most substantial peaks in the data when compared to ChIP-seq.
The study presents the first systematic comparison of the two most common techniques used to analyse histone modifications. The team have collated the results of their experimental and computational optimisations which can serve as guidelines for researchers wanting to profile histone modification.
Adapted from an article on the UK DRI website.
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Senior Lecturer in Neuroscience