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Single-Cell Factor Localization on Chromatin using Ultra-Low Input Cleavage Under Targets and Release using Nuclease
Published on: February 1, 2022
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Multifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag
Michael P Meers1,2, Geneva Llagas1, Derek H Janssens1
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Nature Biotechnology
|November 1, 2022
Summary
Multiple Target Identification by Tagmentation (MulTI-Tag) allows simultaneous profiling of multiple chromatin features in single cells. This method enables detailed characterization of cell types and regulatory landscapes in development and disease.
Area of Science:
- Epigenetics and Genomics
- Cell Biology
- Molecular Biology
Background:
- Chromatin profiling is crucial for understanding cell identity and development.
- Mapping multiple chromatin-associated proteins in single cells is technically challenging.
- Existing methods limit the simultaneous analysis of diverse epigenetic marks.
Purpose of the Study:
- To develop a novel antibody barcoding approach for simultaneous, high-resolution chromatin profiling in single cells.
- To enable the detection of multiple histone modifications within the same cell.
- To advance the comprehensive characterization of cell-specific gene regulatory landscapes.
Main Methods:
- Development and optimization of Multiple Target Identification by Tagmentation (MulTI-Tag).
- Antibody barcoding strategy for simultaneous detection of chromatin features.
- Application to single-cell analysis of histone modifications (H3K27me3, H3K4me1/2, H3K36me3).
Main Results:
- MulTI-Tag successfully profiles up to three histone modifications simultaneously in single cells with high sensitivity and specificity.
- The method resolves distinct cell types and developmental trajectories.
- Identified coordinated patterns of active and repressive regulatory element usage during differentiation.
- Revealed novel associations between different histone marks.
Conclusions:
- MulTI-Tag provides a powerful tool for multifactorial epigenetic profiling in single cells.
- This approach enhances the resolution of cell-specific gene regulatory landscapes.
- It holds significant promise for studying development, cell differentiation, and disease mechanisms.

