Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization
PLOS GENETICS(2021)
摘要
Author summary Courtship behavior in male Drosophila melanogaster is controlled by a well-defined neural circuit that is labeled by the male-specific transcription factor Fruitless (Fru(M)). While Fru(M) is known to change the number, anatomy and connectivity of neurons which comprise the circuit and has been suggested to repress the expression of a few gene targets, the mechanism of how Fru(M) regulates genes across many different kinds of neurons is unknown. Using an approach to identify gene regulatory elements based on their chromatin accessibility states (ATAC-seq), we identified a large set of chromatin accessibility changes downstream of Fruitless. By examining the activity of these regulatory elements in-vivo, we found that their activity was 1) sexually dimorphic and 2) specific to a single class of Fru(M) neurons, suggesting that Fru(M) acts on different chromatin targets in different neuron classes comprising the courtship circuit. Further, we found a known Fru(M)-regulated enhancer of the Fru(M)-repressed gene Lgr3 to have closed chromatin specifically in Fru(M) neurons. Combined with an enrichment of Fru(M) motifs in regions which are closed in Fru(M) neurons, we present a mechanism where Fru(M) directs the decommissioning of sex-shared regulatory elements to masculinize neurons in a cell-type specific manner. In the fruit fly Drosophila melanogaster, male-specific splicing and translation of the Fruitless transcription factor (Fru(M)) alters the presence, anatomy, and/or connectivity of >60 types of central brain neurons that interconnect to generate male-typical behaviors. While the indispensable function of Fru(M) in sex-specific behavior has been understood for decades, the molecular mechanisms underlying its activity remain unknown. Here, we take a genome-wide, brain-wide approach to identifying regulatory elements whose activity depends on the presence of Fru(M). We identify 436 high-confidence genomic regions differentially accessible in male fruitless neurons, validate candidate regions as bona-fide, differentially regulated enhancers, and describe the particular cell types in which these enhancers are active. We find that individual enhancers are not activated universally but are dedicated to specific fru(+) cell types. Aside from fru itself, genes are not dedicated to or common across the fru circuit; rather, Fru(M) appears to masculinize each cell type differently, by tweaking expression of the same effector genes used in other circuits. Finally, we find Fru(M) motifs enriched among regulatory elements that are open in the female but closed in the male. Together, these results suggest that Fru(M) acts cell-type-specifically to decommission regulatory elements in male fruitless neurons.
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要