UMass Chan Medical School Faculty Publications

UMMS Affiliation

Department of Molecular, Cell, and Cancer Biology; Program in Bioinformatics and Integrative Biology; Program in Systems Biology; Graduate School of Biomedical Sciences; Garber Lab

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Article Preprint


Amino Acids, Peptides, and Proteins | Bioinformatics | Cell Biology | Genomics | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides


Methods derived from CUT&RUN and CUT&Tag 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 colocalization of different chromatin proteins in the same cells and requiring prioritization of targets where samples are limiting. Here we describe multi-CUT&Tag, an adaptation of CUT&Tag that overcomes these hurdles by using antibody-specific barcodes to simultaneously map multiple proteins in the same cells. Highly specific multi-CUT&Tag 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-CUT&Tag profiling facilitated identification of distinct cell types from a mixed population and characterization of cell type-specific chromatin architecture. In sum, multi-CUT&Tag increases the information content per cell of epigenomic maps, facilitating direct analysis of the interplay of different proteins on chromatin.


Genomics, chromatin proteins, multi-CUT&Tag mapping

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

DOI of Published Version



bioRxiv 2021.04.27.441642; doi: Link to preprint on bioRxiv.


This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Related Resources

Now published in Molecular Cell, doi: 10.1016/j.molcel.2021.09.019. Link to article on publisher's site

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.