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mChIP-seq for high-throughput epigenomic profiling reveals a decoupling of H2A.Z and H3K4me3 in cancer

GSE280574 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 576 samples Submitted 2026/08/05 Platform GPL29480Platform GPL24676
Summary
Histone variant H2A.Z has multiple roles in regulating gene transcription and its overexpression has been observed in various cancer types. However, the epigenomic characterization of H2A.Z in cancer is unclear. Combining the pool-and-split strategy with sequencing, we developed mChIP-seq, a multiplexed chromatin immunoprecipitation followed by sequencing method to efficiently profile multifactorial epigenetic landscapes of histone marks for multiple samples in parallel. mChIP-seq generates high-quality profiles comparable to standard ChIP-seq but with merits of high efficiency, low cost, and low-input requirement. Using mChIP-seq to profile H2A.Z and 10 H3 histone modifications for 24 cancer cell lines spanning 9 cancer types, we generated 528 epigenomic profiles from two workflows, comprehensively characterized genomic distribution of H2A.Z, and revealed its associations with main histone modifications and gene expression. Moreover, compared with normal cells by integration analysis of public data, we found a decoupling of H2A.Z and H3K4me3 at promoter sites in cancer cells, where the signal intensity of H2A.Z is not in line with the signal intensity of H3K4me3, which further dysregulates gene expression. Altogether, our results demonstrate that mChIP-seq is a powerful technology for epigenomic profiling and reveal abnormal regulatory features of H2A.Z in cancer.
Published in
mChIP-seq for Multiplex and Multifactorial Epigenomic Profiling Uncovers Cancer-specific Histone Features in Cellular and Circulating Nucleosomes
Sun C, Zhang Q, Yan J et al. · bioRxiv : the preprint server for biology 2026 · PMID 42094403 · doi:10.64898/2026.04.27.721226
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Direct links to NCBI, no account and no request form: the whole study as GSE280574_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 576 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1179441 and SRA study SRP541848. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

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