Fig. 5: Schema depicting NSD2’s role in loading the AR enhanceosome at tumor-enriched chimeric AR neo-enhancer elements. | Nature Genetics

Fig. 5: Schema depicting NSD2’s role in loading the AR enhanceosome at tumor-enriched chimeric AR neo-enhancer elements.

From: NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis

Fig. 5

Chromatin loading of AR in prostate epithelial cells follows two distinct modes of DNA interactions: Left: NSD2-independent binding at cis-elements harboring the canonical, 15 bp palindromic AREs that are predominantly found in the physiological/normal enhancer circuitry, and Right: NSD2-dependent loading at cis-regulatory elements harboring chimeric AR half-motifs juxtaposed to the FOXA1 sequence that distinctively constitute the PCa-specific enhancer/super-enhancer (that is, AR neo-enhancer) circuitries. NSD1, partly supported by NSD2, counteracts repressive activity of the PRC2/EZH2 complex, thus further amplifying AR/MYC gene expression programs in mCRPC cells.

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