bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Дек. 3, 2024
ABSTRACT p63 is a clinically-relevant transcription factor heavily involved in development and disease. Mutations the DNA-binding domain lead to severe developmental defects overexpression of plays role progression epithelial-associated cancers. Unraveling specific biochemical mechanisms underlying these phenotypes made challenging by presence multiple isoforms their shared unique contributions Here, we explore function ΔNp63ɑ ΔNp63β determine contribution C-terminal splice variants on known molecular activities. Using RNA-seq ChIP-seq isoform-specific cell lines, show that regulates both canonical targets set genes with varying biological functions. We demonstrate majority genomic binding sites are shared, however enhancer-associated histone modification H3K27ac highly enriched at relative ΔNp63ɑ. An array mutants demonstrates importance domains regulating Our results provide novel insight into differential activities suggest future directions for dissecting functional relevance other
Язык: Английский