biostudies-literatureAcke AKU LeuvenKU Leuven Research CouncilFlemish GovernmentFWOe100https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508849biostudies-literatureUnknown50(17)Interactions between epigenetic readers and histone modifications play a pivotal role in gene expression regulation and aberrations can enact etiopathogenic roles in both developmental and acquired disorders like cancer. Typically, epigenetic interactions are studied by mass spectrometry or chromatin immunoprecipitation sequencing. However, in these methods, spatial information is completely lost. Here, we devise an expansion microscopy based method, termed Expansion Microscopy for Epigenetics or ExEpi, to preserve spatial information and improve resolution. We calculated relative co-localization ratios for two epigenetic readers, lens epithelium derived growth factor (LEDGF) and bromodomain containing protein 4 (BRD4), with marks for heterochromatin (H3K9me3 and H3K27me3) and euchromatin Nucleic acids researchExpansion microscopy allows high resolution single cell analysis of epigenetic readers.PMC950884911B1119N1193720NCASAS2Meth/15/041S17818NC14/17/095-3M170311SBO-SaphirIDN/19/039G0A5316NVoet TVitale RVan Belle SDebyser ZLouis BAcke ARocha SHofkens JfalseExpansion microscopy allows high resolution single cell analysis of epigenetic readers.Interactions between epigenetic readers and histone modifications play a pivotal role in gene expression regulation and aberrations can enact etiopathogenic roles in both developmental and acquired disorders like cancer. Typically, epigenetic interactions are studied by mass spectrometry or chromatin immunoprecipitation sequencing. However, in these methods, spatial information is completely lost. Here, we devise an expansion microscopy based method, termed Expansion Microscopy for Epigenetics or ExEpi, to preserve spatial information and improve resolution. We calculated relative co-localization ratios for two epigenetic readers, lens epithelium derived growth factor (LEDGF) and bromodomain containing protein 4 (BRD4), with marks for heterochromatin (H3K9me3 and H3K27me3) and euchromatin 2022-01-01T00:00:00Z2022 Sep2025-04-18T20:57:55.543Z2025-04-07T08:56:06.901ZS-EPMC95088493571612510.1093/nar/gkac521