RT Journal Article SR Electronic T1 Multifactorial chromatin regulatory landscapes at single cell resolution JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.08.451691 DO 10.1101/2021.07.08.451691 A1 Michael P. Meers A1 Derek H. Janssens A1 Steven Henikoff YR 2021 UL http://biorxiv.org/content/early/2021/07/09/2021.07.08.451691.abstract AB Chromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare distinct chromatin-associated proteins within the same sample. Here we describe a scalable antibody barcoding approach for profiling multiple chromatin features simultaneously in the same individual cells, Multiple Target Identification by Tagmentation (MulTI-Tag). MulTI-Tag is optimized to retain high sensitivity and specificity of enrichment for multiple chromatin targets in the same assay. We use MulTI-Tag to resolve distinct cell types using multiple chromatin features on a commercial single-cell platform, and to distinguish unique, coordinated patterns of active and repressive element regulatory usage in the same individual cells. Multifactorial profiling allows us to detect novel associations between histone marks in single cells and holds promise for comprehensively characterizing cell-specific gene regulatory landscapes in development and disease.Competing Interest StatementS.H. has filed patent applications related to this work.