This is a ChIP-seq protocol that uses native chromatin plus MNase digestion, and employs ligation of a barcoded adapter with a T7 promoter after MNase digestion and prior to the immunoprecipitation step. Due to the barcode on the ligated adapter, we have the option to mix multiple (typically 2 to 4) chromatin preps together, prior to the the immunopreciptation step. This adapter barcode becomes an "in-line" barcode, which is read during the first 8 cycles of Read 2 during the paired-end Illumina sequencing. Subsequent to the recovery of ChIP DNA, we will use the T7 promoter contained within the ligated adapter to in vitro transcribe the ChIP DNA, followed by reverse transcription and PCR amplification, to complete library construction. The PCR amplification incorporates a conventional Illumina barcode, typically one per antibody in use; primer designs are supplied for both single index and dual index Illumina sequencing. We find this protocol gives excellent results with about 50,000 cells per ChIP using antibodies to histone modifications. This protocol extends the method previously published (van Galen et al, 2016). While conceptually similar to the prior method, it differs in several ways from the prior publication, and 100% of the oligonucleotides have been redesigned to achieve higher efficiency.