siQ-ChIP: A reverse-engineered quantitative framework for ChIP-sequencing

Abstract

Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is a key technique for mapping the distribution and relative abundance of histone posttranslational modifications (PTMs) and chromatin-associated factors across genomes. There is a perceived challenge regarding the ability to quantitatively plot ChIP-seq data, and as such, approaches making use of exogenous additives, or "spike-ins" have recently been developed. Relying on the fact that the IP step of ChIP-seq is a competitive binding reaction, we present a quantitative framework for ChIP-seq analysis that circumvents the need to modify standard sample preparation pipelines with spike-in reagents. We also introduce a visualization technique that, when paired with our formal developments, produces a much more rich characterization of sequencing data.

Select EZH2 inhibitors enhance the viral mimicry effects of DNMT inhibition through a mechanism involving calcium-calcineurin-NFAT signaling

“…Using our recently developed sans spike-in quantitative ChIP-seq method (siQ-ChIP) (89,90), we next quantified changes in H3K27me3 following drug exposure (Figure S4D-G). TAZ treatment, alone and in combination with DAC, significantly reduced H3K27me3 levels across the genome following 3 days of treatment (Figure 4A).…”