Cell identity is driven through the selective expression of transcription factors (TFs) that cooperate with chromatin regulators to establish unique gene expression programs. Consequently, chromatin factors are commonly viewed as ubiquitously expressed and generic, accessory facilitators of the transcriptional process rather than lineage defining. However, dysregulation of chromatin factors has emerged as a major class of oncogenic drivers in many cancers, including haematopoietic malignancies, highlighting their capacity to exert specific and selective effects on gene regulation. What remains unclear is whether the expression of chromatin factors themselves, much like TFs, is selectively regulated across normal human tissues and how this regulation is altered in cancer.
Here, we systematically analysed publicly available gene expression datasets from the Human Protein Atlas (HPA) to define patterns of chromatin factor expression across normal tissues, single-cell populations and cancer cell lines. By quantifying expression variability across cell and tissue types, we identified distinct classes of chromatin factors and tissues that are specifically enriched relative to other gene categories.
To determine the functional relevance of these expression patterns in cancer, we integrated chromatin factor expression data with genome-scale dependency profiles from the Cancer Dependency Map (DepMap). This analysis revealed relationships between chromatin factor expression and cancer cell survival, uncovering novel tumour-selective vulnerabilities. Finally, by correlating genome-wide expression patterns with dependency data, we will also identify candidate synthetic lethal interactions with potential therapeutic relevance.
Together, this project aims to challenge the prevailing view of chromatin factors as uniformly expressed regulators and provide a framework for identifying predictive chromatin biomarkers and pharmacological targets across distinct tissue and cancer contexts.