Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization
| Autor: | E. Josephine Clowney, Margarita V. Brovkina, Abbigayl E. C. Burtis, Rachel Duffié |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Gene Expression QH426-470 Nervous System Animals Genetically Modified Cell Signaling Animal Cells Neural Pathways Medicine and Health Sciences Drosophila Proteins RNA-Seq Regulatory Elements Transcriptional Genetics (clinical) Regulation of gene expression Neurons biology Effector Chromosome Biology Drosophila Melanogaster Eukaryota Brain Animal Models Genomics Chromatin Insects Experimental Organism Systems RNA splicing fruitless Drosophila Epigenetics Female Drosophila melanogaster Cellular Types Anatomy Genomic Signal Processing Research Article Signal Transduction Cell type Arthropoda Nerve Tissue Proteins Research and Analysis Methods Model Organisms Sex Factors Dosage Compensation Genetic Genetics Animals Gene Regulation Enhancer Molecular Biology Gene Transcription factor Ecology Evolution Behavior and Systematics Organisms Biology and Life Sciences Cell Biology biology.organism_classification Invertebrates Neuroanatomy Gene Expression Regulation Cellular Neuroscience Animal Studies Neuroscience Zoology Entomology Genome-Wide Association Study Transcription Factors |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 17, Iss 2, p e1009338 (2021) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | In the fruit fly Drosophila melanogaster, male-specific splicing and translation of the Fruitless transcription factor (FruM) 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 FruM 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 FruM. 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, FruM appears to masculinize each cell type differently, by tweaking expression of the same effector genes used in other circuits. Finally, we find FruM motifs enriched among regulatory elements that are open in the female but closed in the male. Together, these results suggest that FruM acts cell-type-specifically to decommission regulatory elements in male fruitless neurons. 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 (FruM). While FruM 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 FruM 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 FruM neurons, suggesting that FruM acts on different chromatin targets in different neuron classes comprising the courtship circuit. Further, we found a known FruM-regulated enhancer of the FruM-repressed gene Lgr3 to have closed chromatin specifically in FruM neurons. Combined with an enrichment of FruM motifs in regions which are closed in FruM neurons, we present a mechanism where FruM directs the decommissioning of sex-shared regulatory elements to masculinize neurons in a cell-type specific manner. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |