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MYC-FACT Interactions Drive Z-DNA Formation to Modulate Transcriptional Dynamics [RNA-seq]

GSE290661 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/11/18 Platform GPL24676
Summary
DNA topology is critical for regulating transcription and maintaining cellular homeostasis. Z-DNA is a left-handed DNA helix in regions with high transcriptional activity. Its physiological function remains poorly understood. Here, we demonstrate that oncoprotein MYC induces the formation of Z-DNA by recruiting the chromatin remodeler FACT, independent of RNA Polymerase II activity. FACT facilitates Z-DNA formation by remodeling H2A/H2B dimers within intact nucleosomes. Additionally, the phosphorylation of FACT regulates its liquid-liquid phase separation, promoting its efficient recruitment to chromatin by MYC. Through a genome-wide analysis and characterization of engineered Z-DNA promoters, we found that Z-DNA directly facilitates the loading of RNA Polymerase II, thereby promoting transcriptional activity. This study elucidates the molecular mechanisms of Z-DNA dynamics and emphasizes its functional importance in transcriptional regulation, providing insights into the role of non-B-DNA structures in chromatin biology and MYC-driven cancer.
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Also filed as BioProject PRJNA1229501 and SRA study SRP566842. Searching any of these in the dataset finder brings you back here.

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