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Combinatorial single-cell profiling of all major chromatin types with MAbID

bioRxiv, ISSN: 2692-8205
2023
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Article Description

Gene expression programs result from the collective activity of many regulatory factors. To obtain insight into the mechanisms that govern gene regulation, it is imperative to study their combined mode of action and interconnectivity. However, it has been challenging to simultaneously measure a combination of these factors within one sample. Here, we introduce MAbID, a method that combines genomic profiling of many histone modifications and chromatin-binding proteins in a single reaction. MAbID employs antibody-DNA conjugates to enable genomic barcoding of chromatin at sites of epitope occupancy. This barcoding strategy allows for the combined incubation of multiple antibodies in a single sample to reveal the genomic distributions of many epigenetic states simultaneously. We used MAbID to profile both active and inactive chromatin types in human cell lines and multiplexed measurements in the same sample without loss of data quality. Moreover, we obtained joint measurements of six epitopes covering all major chromatin types in single cells during mouse in vitro neural differentiation and captured associated changes in multifactorial chromatin states. Thus, MAbID holds the potential to gain unique insights into the interplay between gene regulatory mechanisms, especially in settings with limited sample material and in single cells.

Bibliographic Details

Silke J.A. Lochs; Robin H. van der Weide; Kim L. de Luca; Tessy Korthout; Ramada E. van Beek; Jop Kind; Hiroshi Kimura

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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