Nucleic acid constructs and methods for labeling and detecting nucleosomal DNA modifications

A method for labeling nucleic acids from a cell or population of cells comprising:

• providing one or more individual discrete volumes, each individual discrete volume comprising a cell or population of cells;
• lysing the cell or population of cells in each individual discrete volume and fragmenting nucleosomal DNA from the lysed cell or population of cells;
• labeling the fragmented nucleosomal DNA in each individual discrete volume with a barcoded adapter on at least one free end of the fragmented nucleosomal DNA, wherein:
• the barcoded adapter comprises an amplification promoter adjacent to a first or second read sequencing primer binding site which is adjacent to a barcode sequence,
• the labeled nucleosomal DNA comprises, in a 3′ to 5′ orientation, a first read sequencing primer binding site, the nucleosomal DNA sequence, the barcode sequence, and a second read sequencing primer binding site,
• the barcode sequence is unique to each individual discrete volume thereby identifying a sample from which the labeled nucleosomal DNA originated;
• isolating and sequencing the labeled nucleosomal DNA from each sample;
• and
• grouping the sequenced nucleosomal DNA by common barcode thereby identifying the individual discrete volumes from which the nucleosomal DNA originated.