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Multiplexed Chromatin Profiling at Scale: Resolving Chromatin Responses Across Conditions, Pertubations, and Cell States [ASHG 2026]

Access this poster presented by Active Motif Head of R&D Brian Egan at ASBMB Transcriptional Regulation by Chromatin and RNA Polymerase 2026 Meeting, outlining applications of TIP-ChIP, our new method designed to reduce cell number requirements, increase throughput, and minimize sample-to-sample variability compared to traditional ChIP.

Quantitative chromatin profiling requires experiments that compare many biological conditions with sufficient replication to distinguish true biological change from technical noise. Conventional ChIP-Seq, CUT&Tag, and CUT&RUN workflows process each sample as an independent immunoprecipitation, so hands-on time, cost, and tube-to-tube technical variability all increase with sample number, placing practical limits on the number of conditions, time points, or replicates a study can include.

TIP-ChIP addresses this by moving sample multiplexing upstream of the immunoprecipitation: barcoded chromatin from individual samples is pooled and processed together across multiple parallel IP reactions, allowing up to 96 samples to be profiled in a single experiment. Because technical variability is shared within each pool, this provides relative quantitation, reduced background, and removes the need for exogenous spike-in, since global changes are retained within the pool. We demonstrate this approach in three applications: dose-dependent H3K27me3 loss and reciprocal H3K27ac gain following EZH2 inhibition; a single-reaction epigenome-editing screen resolving guide on-/off - target specificity and target-gene transcription; and dynamic NF-κB p50 occupancy with associated histone PTM and transcriptional changes across an LPS stimulation time course.

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