Multifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag

Michael P. Meers, Geneva Llagas, Derek H. Janssens, Christine A. Codomo, Steven Henikoff

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Chromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare different chromatin-associated proteins in the same sample. Here we describe Multiple Target Identification by Tagmentation (MulTI-Tag), an antibody barcoding approach for profiling multiple chromatin features simultaneously in single cells. We optimized MulTI-Tag to retain high sensitivity and specificity, and we demonstrate detection of up to three histone modifications in the same cell: H3K27me3, H3K4me1/2 and H3K36me3. We apply MulTI-Tag to resolve distinct cell types and developmental trajectories; to distinguish unique, coordinated patterns of active and repressive element regulatory usage associated with differentiation outcomes; and to uncover associations between histone marks. Multifactorial epigenetic profiling holds promise for comprehensively characterizing cell-specific gene regulatory landscapes in development and disease.

Original languageEnglish
Pages (from-to)708-716
Number of pages9
JournalNature Biotechnology
Issue number5
StatePublished - May 2023


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