Combinatorial single-cell profiling of major chromatin types with MAbID

Gene expression programs result from the collective activity of numerous regulatory factors. Studying their cooperative mode of action is imperative to understand gene regulation, but simultaneously measuring these factors within one sample has been challenging. Here, we introduce MAbID, a method for combinatorial genomic profiling of histone modifications and chromatin-binding proteins. MAbID employs antibody-DNA conjugates to insert genomic barcodes at sites of epitope occupancy, enabling combined incubation of multiple antibodies to reveal the genomic distributions of many epigenetic markers simultaneously. We used MAbID to profile all major chromatin types and multiplexed measurements without loss of individual data quality. Moreover, we obtained joint measurements of six epitopes in single cells of mouse bone marrow and during mouse in vitro differentiation, capturing associated changes in multifactorial chromatin states. Thus, MAbID holds the potential to gain unique insights into the interplay between gene regulatory mechanisms, especially for low-input samples and in single cells. Overall design: Epigenomic profiling using antibody-conjugates in K562, mESC, early differentiating mNPC, and bone-marrow samples.