There are several methods that have been developed to perform ChiP assays with FFPE tissue samples. 

One method is PAT-ChIP, which involves a combination of micrococcal nuclease (MNase) digestion and sonication in combination with a high concentration of SDS. 

Another method is FiT-seq, which involves heating at 40°C for 1 hour, proteinase K treatment, and sonication to enhance chromatin extraction. 

Researchers in one study also developed a new method called Chrom-EX PE technology to extract chromatin from FFPE tissues. This method enhances the yield of soluble chromatin while enabling controlled preparation. A tissue-level cross-link reversal step is used to overcome challenges associated with over-fixed chromatin. The approach achieved approximately 70–90% soluble chromatin yield from mouse FFPE tissues. The isolated chromatin was efficient with ChIP-seq for histone marks and chromatin-associated proteins. Additionally, chromatin prepared using Chrome-EX PE exhibited a fragmentation pattern with varying incubation temperatures. This approach offers a way to obtain high-quality chromatin for ChIP-seq without subjecting the sample to harsh treatments and holds potential for developing other chromatin-based epigenetic assays.