Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.

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 funct...

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Main Authors: Margarita V Brovkina, Rachel Duffié, Abbigayl E C Burtis, E Josephine Clowney
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-02-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1009338
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spelling doaj-beece1950b874fd1a999cce950785fa92021-06-25T04:30:35ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-02-01172e100933810.1371/journal.pgen.1009338Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.Margarita V BrovkinaRachel DuffiéAbbigayl E C BurtisE Josephine ClowneyIn 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.https://doi.org/10.1371/journal.pgen.1009338
collection DOAJ
language English
format Article
sources DOAJ
author Margarita V Brovkina
Rachel Duffié
Abbigayl E C Burtis
E Josephine Clowney
spellingShingle Margarita V Brovkina
Rachel Duffié
Abbigayl E C Burtis
E Josephine Clowney
Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
PLoS Genetics
author_facet Margarita V Brovkina
Rachel Duffié
Abbigayl E C Burtis
E Josephine Clowney
author_sort Margarita V Brovkina
title Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
title_short Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
title_full Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
title_fullStr Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
title_full_unstemmed Fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
title_sort fruitless decommissions regulatory elements to implement cell-type-specific neuronal masculinization.
publisher Public Library of Science (PLoS)
series PLoS Genetics
issn 1553-7390
1553-7404
publishDate 2021-02-01
description 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.
url https://doi.org/10.1371/journal.pgen.1009338
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