Single-cell profiling of transcriptome and histone modifications with EpiDamID.

Area of Science:

• Epigenetics
• Molecular Biology
• Genomics

Background:

• Single-cell sequencing advances allow multi-modal measurements.
• Simultaneous detection of histone modifications and transcription at single-cell resolution is challenging.

Purpose of the Study:

• Introduce EpiDamID, a novel experimental approach.
• Enable genome-wide identification of histone post-translational modifications.
• Facilitate joint measurement of chromatin marks and transcription at single-cell resolution.

Main Methods:

• Leverage single-chain variable fragment antibodies, engineered chromatin reader domains, and endogenous chromatin-binding proteins.
• Adapt DamID technology for histone modification mapping.
• Apply EpiDamID to profile Polycomb occupancy and H3K9me3.

Main Results:

• Demonstrate EpiDamID's compatibility with genome-wide histone modification detection.
• Provide evidence for hierarchical gene regulatory networks via single-cell Polycomb occupancy profiling.
• Map H3K9me3 in zebrafish embryogenesis, identifying notochord-specific heterochromatin.

Conclusions:

• EpiDamID is a valuable new tool for studying chromatin states in dynamic cellular processes.
• The method facilitates a deeper understanding of epigenetic regulation at single-cell resolution.
• EpiDamID opens new avenues for investigating developmental biology and gene regulation.