Diaz-Saldana, P. P. | bioRxiv Science

bioRxiv2023

Sequence reliance of a Drosophila context-dependent transcription factor

Despite binding similar cis elements in multiple locations, a single transcription factor often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent transcription factor CLAMP targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, loci-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.

genetics↗

bioRxiv2022

MSL2 targets histone genes in Drosophila virilis

Histone genes are amongst the most evolutionary conserved in eukaryotic genomes, yet cis-regulatory mechanisms of histone gene regulation differ considerably amongst species. In Drosophila melanogaster, an interaction between GA-rich cis elements in the H3/H4 promoter and the GA-binding transcription factor CLAMP is important for promoting histone gene regulation and factor recruitment to the locus. CLAMP also participates in male dosage compensation by recruiting the Male Specific Lethal Complex (MSLc) to the X-chromosome. We discovered that the male-specific protein of MSLc, MSL2, is recruited to the autosomal major histone locus in D. virilis but not to the minor locus or to the single histone locus in other species. While the histone coding sequences are well conserved between species, the critical GA-rich cis elements in the H3/H4 promoter are poorly conserved between D. melanogaster and D. virilis. We show that CLAMP still targets the two D. virilis histone loci in vivo. Further, CLAMP interacts with the D. virilis H3/H4 promoter in vitro, even when the poorly-conserved GA-rich cis elements are deleted, indicating that the protein interacts differently with the D. virilis promoter than it does with the D. melanogaster promoter. Since CLAMP and MSL2 directly interact in D. melanogaster, we propose that D. virilis CLAMP recruits MSL2 to an ectopic autosomal site through interaction with X-like cis elements. Further, localization of MSL2 to one of the D. virilis histone loci suggests that the loci are regulated differently and that males and females have different requirements for histone gene regulation.

genetics↗