Galouzis, C. C. | Search bioRxiv

bioRxiv2025

Chip (Ldb1) is a new cofactor of Zelda forming a functional bridge to CBP during zygotic genome activation

The cofactor Ldb1 (Chip) is linked to many processes in gene regulation, including enhancer-promoter communication, inter-chromosomal interactions and enhanceosome-cofactor-like activity. However, its functional requirement and molecular role during embryogenesis has not been assessed to date. Here, we used optogenetics (iLEXY), to rapidly deplete Drosophila Ldb1 (Chip) from the nucleus at precise time windows. Remarkably, this pinpointed the essential window of Chips function in just one-hour of embryogenesis, overlapping zygotic genome activation (ZGA). We show that Zelda, a pioneer factor essential for ZGA, recruits Chip to chromatin, and both factors regulate concordant changes in gene expression, suggesting that Chip is a cofactor of Zelda. Surprisingly, Chip is not required for chromatin architecture at these stages, instead it recruits CBP, and is essential for the placement of H3K27ac. Taken together, our results identify Chip (Ldb1) as a functional bridge between Zelda and the coactivator CBP to regulate gene expression in early embryogenesis.

genomics↗

bioRxiv2020

trans-homolog interaction regulates the sex-biased expression of an X-linked gene

Sex-biased gene expression patterns in animals are generally controlled by the somatic sex-determination hierarchies. How the different tiers of these hierarchies act on sexually dimorphic gene regulation is still poorly understood. In the developing Drosophila biarmipes wing, the X-linked gene yellow is expressed in males in a specific distal spot pattern that prefigures a corresponding adult pigmentation pattern. This yellow expression pattern is controlled by the spot enhancer, but the origin of yellow sexually dimorphic expression is unknown. Here we find that the functional interaction between homologous yellow alleles silences specifically the spot enhancer, which is therefore active in males (XY) but not in females (XX). We show that inserting yellow at homologous positions on autosomes recapitulates, in either sex, the homologous-dependent silencing of the spot enhancer. We further find that this silencing requires the yellow intron as well as the architectural protein Mod(mdg4). Finally, we show that Mod(mdg4) is also necessary for the sex-biased expression of some X-linked genes in the brain. Our results demonstrate that regulatory interactions between X-linked homologous alleles promote their sex-biased expression, independently of the canonical sex-determination hierarchy. More generally, they illustrate the biological significance of homologous chromosome pairing and trans-homolog interactions for the sexually dimorphic regulation of X-linked genes.

genetics↗