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

Abstract

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
Volume41
Issue number5
DOIs
StatePublished - May 2023

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