Human ERG oncoprotein represses <i>a Drosophila</i> LIM domain binding protein-coding gene <i>Chip</i>.

ABSTRACT: Human ETS Related Gene, ERG, a master transcription factor, turns oncogenic upon its out-of-context activation in diverse developmental lineages. However, the mechanism underlying its lineage-specific activation of Notch (N), Wnt, or EZH2-three well-characterized oncogenic targets of ERG-remains elusive. We reasoned that deep homology in genetic tool kits might help uncover such elusive cancer mechanisms in Drosophila. By heterologous gain of human ERG in Drosophila, here we reveal Chip, which codes for a transcriptional coactivator, LIM-domain-binding (LDB) protein, as its novel target. ERG represses Drosophila Chip via its direct binding and, indirectly, via E(z)-mediated silencing of its promoter. Downregulation of Chip disrupts LI

SUBMITTER: Bharti M 

PROVIDER: S-EPMC9926275 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature