RT Journal Article SR Electronic T1 Multiplexed single-cell profiling of chromatin states at genomic loci by expansion microscopy JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.17.385476 DO 10.1101/2020.11.17.385476 A1 Marcus A. Woodworth A1 Kenneth K.H. Ng A1 Aaron R. Halpern A1 Nicholas A. Pease A1 Phuc H.B. Nguyen A1 Hao Yuan Kueh A1 Joshua C. Vaughan YR 2020 UL http://biorxiv.org/content/early/2020/11/18/2020.11.17.385476.abstract AB Proper regulation of genome architecture and activity is essential for the development and function of multicellular organisms. Histone modifications, acting in combination, specify these activity states at individual genomic loci. However, the methods used to study these modifications often require either a large number of cells or are limited to targeting one histone mark at a time. Here, we developed a new method called Single Cell Evaluation of Post-TRanslational Epigenetic Encoding (SCEPTRE) that uses Expansion Microscopy (ExM) to visualize and quantify multiple histone modifications at non-repetitive genomic regions in single cells at a spatial resolution of ~75 nm. Using SCEPTRE, we distinguished multiple histone modifications at a single housekeeping gene, quantified histone modification levels at multiple developmentally-regulated genes in individual cells, and identified a relationship between histone H3K4 trimethylation and the loading of paused RNA polymerase II at individual loci. Thus, SCEPTRE enables multiplexed detection of combinatorial chromatin states at single genomic loci in single cells.Competing Interest StatementThe authors have declared no competing interest.