Azad Alizada, Aline Martins, Nolwenn Mouniee, Julia Rodriguez Suarez, Benjamin Bertin, Nathalie Gueguen, Vincent Mirouse, Stephanie Maupetit Mehouas, Austin J Rivera, Nelson C. Lau, Gregory J Hannon, Benjamin Czech Nicholson, Emilie Brasset
{"title":"转录因子 Traffic jam 协调果蝇卵巢中的体细胞 piRNA 通路","authors":"Azad Alizada, Aline Martins, Nolwenn Mouniee, Julia Rodriguez Suarez, Benjamin Bertin, Nathalie Gueguen, Vincent Mirouse, Stephanie Maupetit Mehouas, Austin J Rivera, Nelson C. Lau, Gregory J Hannon, Benjamin Czech Nicholson, Emilie Brasset","doi":"10.1101/2024.09.10.612307","DOIUrl":null,"url":null,"abstract":"Transposable elements (TEs) pose a threat to genome integrity, and the piRNA pathway in animal gonads plays a crucial role in silencing TE activity. While the transcriptional regulation of the piRNA pathway components in germ cells has been documented in mice and flies, the mechanisms orchestrating the transcriptional program of the somatic piRNA pathway in Drosophila ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), an orthologue of a large Maf transcription factor in mammals, is a master regulator of the piRNA pathway in ovarian somatic cells, playing a crucial role in maintaining TE silencing and genomic integrity in somatic tissues. We show that Tj directly binds to the promoters of somatic-enriched piRNA factors such as fs(1)Yb, nxf2, panx, and armi, as well as the flamenco piRNA cluster, a major locus for TE silencing in somatic cells. Depletion of Tj in somatic follicle cells results in a significant downregulation of these piRNA factors, a complete loss of flam expression and de-repression of gypsy-family TEs, which have gained the ability to activate in ovarian somatic cells allowing them to infect germ cells and be transmitted to future generations. We have identified an enhancer carrying Tj binding motifs located downstream of the flam promoter that is essential for robust and tissue-specific flam expression in somatic follicle cells of the adult ovary. This work uncovers a previously unappreciated layer of transcriptional regulation of the piRNA pathway, and we propose that the arms race between the host and TEs has driven the evolution of promoters in piRNA genes and clusters to respond to a unique transcription factor thereby ensuring efficient silencing of gypsy-family TEs","PeriodicalId":501108,"journal":{"name":"bioRxiv - Molecular Biology","volume":"100 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The transcription factor Traffic jam orchestrates the somatic piRNA pathway in Drosophila ovaries\",\"authors\":\"Azad Alizada, Aline Martins, Nolwenn Mouniee, Julia Rodriguez Suarez, Benjamin Bertin, Nathalie Gueguen, Vincent Mirouse, Stephanie Maupetit Mehouas, Austin J Rivera, Nelson C. Lau, Gregory J Hannon, Benjamin Czech Nicholson, Emilie Brasset\",\"doi\":\"10.1101/2024.09.10.612307\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Transposable elements (TEs) pose a threat to genome integrity, and the piRNA pathway in animal gonads plays a crucial role in silencing TE activity. While the transcriptional regulation of the piRNA pathway components in germ cells has been documented in mice and flies, the mechanisms orchestrating the transcriptional program of the somatic piRNA pathway in Drosophila ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), an orthologue of a large Maf transcription factor in mammals, is a master regulator of the piRNA pathway in ovarian somatic cells, playing a crucial role in maintaining TE silencing and genomic integrity in somatic tissues. We show that Tj directly binds to the promoters of somatic-enriched piRNA factors such as fs(1)Yb, nxf2, panx, and armi, as well as the flamenco piRNA cluster, a major locus for TE silencing in somatic cells. Depletion of Tj in somatic follicle cells results in a significant downregulation of these piRNA factors, a complete loss of flam expression and de-repression of gypsy-family TEs, which have gained the ability to activate in ovarian somatic cells allowing them to infect germ cells and be transmitted to future generations. We have identified an enhancer carrying Tj binding motifs located downstream of the flam promoter that is essential for robust and tissue-specific flam expression in somatic follicle cells of the adult ovary. This work uncovers a previously unappreciated layer of transcriptional regulation of the piRNA pathway, and we propose that the arms race between the host and TEs has driven the evolution of promoters in piRNA genes and clusters to respond to a unique transcription factor thereby ensuring efficient silencing of gypsy-family TEs\",\"PeriodicalId\":501108,\"journal\":{\"name\":\"bioRxiv - Molecular Biology\",\"volume\":\"100 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Molecular Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.09.10.612307\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Molecular Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.10.612307","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
可转座元件(TE)对基因组完整性构成威胁,而动物性腺中的 piRNA 通路在沉默 TE 活性方面起着至关重要的作用。虽然小鼠和苍蝇的生殖细胞中 piRNA 通路成分的转录调控已被记录,但果蝇卵巢中体细胞 piRNA 通路转录程序的协调机制仍未解决。在这里,我们证明了Traffic jam(Tj)是哺乳动物中大型Maf转录因子的直系同源物,是卵巢体细胞中piRNA通路的主调控因子,在维持体细胞组织中的TE沉默和基因组完整性方面起着至关重要的作用。我们的研究表明,Tj 直接与体细胞丰富的 piRNA 因子(如 fs(1)Yb、nxf2、panx 和 armi)的启动子以及 flamenco piRNA 簇(体细胞中 TE 沉默的主要位点)结合。体细胞卵泡中 Tj 的缺失会导致这些 piRNA 因子的显著下调、flam 表达的完全丧失以及吉普赛家族 TEs 的去抑制,而吉普赛家族 TEs 已获得在卵巢体细胞中激活的能力,使其能够感染生殖细胞并传给后代。我们发现了一个位于flam启动子下游、携带Tj结合基序的增强子,它对于flam在成体卵巢体细胞卵泡中的强健表达和组织特异性表达至关重要。这项工作揭示了 piRNA 通路转录调控的一个以前未被认识的层次,我们认为宿主和 TE 之间的军备竞赛推动了 piRNA 基因和基因簇启动子的进化,使其能够对一种独特的转录因子做出反应,从而确保对吉普赛家族 TE 的有效沉默。
The transcription factor Traffic jam orchestrates the somatic piRNA pathway in Drosophila ovaries
Transposable elements (TEs) pose a threat to genome integrity, and the piRNA pathway in animal gonads plays a crucial role in silencing TE activity. While the transcriptional regulation of the piRNA pathway components in germ cells has been documented in mice and flies, the mechanisms orchestrating the transcriptional program of the somatic piRNA pathway in Drosophila ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), an orthologue of a large Maf transcription factor in mammals, is a master regulator of the piRNA pathway in ovarian somatic cells, playing a crucial role in maintaining TE silencing and genomic integrity in somatic tissues. We show that Tj directly binds to the promoters of somatic-enriched piRNA factors such as fs(1)Yb, nxf2, panx, and armi, as well as the flamenco piRNA cluster, a major locus for TE silencing in somatic cells. Depletion of Tj in somatic follicle cells results in a significant downregulation of these piRNA factors, a complete loss of flam expression and de-repression of gypsy-family TEs, which have gained the ability to activate in ovarian somatic cells allowing them to infect germ cells and be transmitted to future generations. We have identified an enhancer carrying Tj binding motifs located downstream of the flam promoter that is essential for robust and tissue-specific flam expression in somatic follicle cells of the adult ovary. This work uncovers a previously unappreciated layer of transcriptional regulation of the piRNA pathway, and we propose that the arms race between the host and TEs has driven the evolution of promoters in piRNA genes and clusters to respond to a unique transcription factor thereby ensuring efficient silencing of gypsy-family TEs