Embryonic stem cell factors DPPA2/4 amplify active H3K4me3-H2AK119ub chromatin domains in non-small cell lung cancer - PubMed
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- #DPPA2/4
- #NSCLC
- #chromatin
- DPPA2/4, embryonic stem cell factors, are re-expressed in non-small cell lung cancer (NSCLC) and linked to poorly differentiated tumors and worse patient outcomes.
- DPPA2/4 multimerize for protein stability and enhanced nucleosome binding, binding CG-rich sequences at promoters of developmental genes, Wnt signaling, and catabolic genes.
- DPPA2/4 preferentially bind active H3K4me3 and H3K27ac chromatin domains, which are also enriched for PRC1 and H2AK119ub, maintaining RING1B and H2AK119ub at these regions.
- Despite PRC2.1 presence, these domains lack H3K27me3, indicating uncoupling between PRC2 recruitment and its catalytic product.
- Overexpression of DPPA2/4 in NSCLC cells promotes active chromatin states and increases tumor growth in xenografts.
- DPPA2/4 act as amplifiers of active and poised chromatin, highlighting how embryonic factors may drive tumorigenesis when reactivated in cancer.