Simultaneous profiling of multiple chromatin proteins in the same cells
Department of Molecular, Cell, and Cancer Biology; Program in Bioinformatics and Integrative Biology; Program in Systems Biology; Garber Lab; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Bioinformatics | Cell Biology | Genomics | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides
Methods derived from CUTandRUN and CUTandTag enable genome-wide mapping of the localization of proteins on chromatin from as few as one cell. These and other mapping approaches focus on one protein at a time, preventing direct measurements of co-localization of different chromatin proteins in the same cells and requiring prioritization of targets where samples are limiting. Here, we describe multi-CUTandTag, an adaptation of CUTandTag that overcomes these hurdles by using antibody-specific barcodes to simultaneously map multiple proteins in the same cells. Highly specific multi-CUTandTag maps of histone marks and RNA Polymerase II uncovered sites of co-localization in the same cells, active and repressed genes, and candidate cis-regulatory elements. Single-cell multi-CUTandTag profiling facilitated identification of distinct cell types from a mixed population and characterization of cell-type-specific chromatin architecture. In sum, multi-CUTandTag increases the information content per cell of epigenomic maps, facilitating direct analysis of the interplay of different chromatin proteins.
H3K27ac, H3K27me3, RNA polymerase, chromatin, histones, profiling, single-cell, transcription
DOI of Published Version
Gopalan S, Wang Y, Harper NW, Garber M, Fazzio TG. Simultaneous profiling of multiple chromatin proteins in the same cells. Mol Cell. 2021 Nov 18;81(22):4736-4746.e5. doi: 10.1016/j.molcel.2021.09.019. Epub 2021 Oct 11. PMID: 34637755; PMCID: PMC8604773. Link to article on publisher's site
Gopalan S, Wang Y, Harper NW, Garber M, Fazzio TG. (2021). Simultaneous profiling of multiple chromatin proteins in the same cells. UMass Chan Medical School Faculty Publications. https://doi.org/10.1016/j.molcel.2021.09.019. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2163