{"doi":"10.1101/2019.12.17.880070","title":"<i>sisterless A</i>\n                  is required for activation of\n                  <i>Sex lethal</i>\n                  in the\n                  <i>Drosophila</i>\n                  germline","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Both somatic cells and germ cells must establish their correct sexual identity for proper gametogenesis. In\n                  <jats:italic>Drosophila,</jats:italic>\n                  sex determination in somatic cells is controlled by the switch gene\n                  <jats:italic>Sex lethal</jats:italic>\n                  (\n                  <jats:italic>Sxl</jats:italic>\n                  ), which is activated in females by the presence of two X chromosomes. Though germline sex determination is much less well understood,\n                  <jats:italic>Sxl</jats:italic>\n                  is also essential for the female identity in germ cells. Loss of\n                  <jats:italic>Sxl</jats:italic>\n                  function in the germline results in ovarian germline tumors, a characteristic of male germ cells developing in a female soma. Further,\n                  <jats:italic>Sxl</jats:italic>\n                  expression is sufficient for XY (male) germ cells to produce eggs when transplanted into XX (female) somatic gonads. As in the soma, the presence of two X chromosomes activates\n                  <jats:italic>Sxl</jats:italic>\n                  in the germline, but the mechanism for “counting” X chromosomes in the germline is thought to be different from the soma. Here we have explored this mechanism at both\n                  <jats:italic>cis</jats:italic>\n                  - and\n                  <jats:italic>trans-</jats:italic>\n                  levels. Our data support the model that the\n                  <jats:italic>Sxl</jats:italic>\n                  “establishment” promoter (\n                  <jats:italic>SxlPE</jats:italic>\n                  ) is activated in a female-specific manner in the germline, as in the soma, but that the timing of\n                  <jats:italic>SxlPE</jats:italic>\n                  activation, and the DNA elements that regulate\n                  <jats:italic>SxlPE,</jats:italic>\n                  are different in the germline. Nevertheless, we find that the X chromosome gene\n                  <jats:italic>sisterless A (sisA),</jats:italic>\n                  which helps activate\n                  <jats:italic>Sxl</jats:italic>\n                  in the soma, is also essential for\n                  <jats:italic>Sxl</jats:italic>\n                  activation in the germline. Loss of\n                  <jats:italic>sisA</jats:italic>\n                  leads causes of Sxl expression in the germline, and to ovarian tumors and germline loss. These defects can be rescued by Sxl expression, demonstrating that\n                  <jats:italic>sisA</jats:italic>\n                  lies upstream of\n                  <jats:italic>Sxl</jats:italic>\n                  in germline sex determination. We conclude that\n                  <jats:italic>sisA</jats:italic>\n                  acts as an X chromosome counting element in both the soma and the germline, but that additional factors regulating female-specific expression of\n                  <jats:italic>Sxl</jats:italic>\n                  in the germline remain to be discovered.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>AUTHOR SUMMARY</jats:title>\n                  <jats:p>\n                    The production of sperm and eggs requires proper sexual identity to be established in both somatic cells and the germ cells, which ultimately produce the gametes. While somatic sex determination has been well studied in a number of organisms, how germ cells establish their sexual identity is much less well understood. In Drosophila, the RNA binding protein Sex lethal (Sxl) is essential for female sexual identity in both the soma and the germline, but its regulation in the germline is thought to be different than in the soma. Here we explore how\n                    <jats:italic>Sxl</jats:italic>\n                    is activated in the germline. We find that the germline uses a different set of DNA elements to control activation of the key sex-specific\n                    <jats:italic>Sxl</jats:italic>\n                    promoter. Nonetheless, one of the activators of\n                    <jats:italic>Sxl</jats:italic>\n                    in the soma, the transcription factor Sisterless A (SisA), also acts to activate\n                    <jats:italic>Sxl</jats:italic>\n                    in the germline. Our data indicate that, while SisA acts as a common activator in both the soma and germline, additional, germline-specific\n                    <jats:italic>Sxl</jats:italic>\n                    activators remain to be discovered.\n                  </jats:p>\n                </jats:sec>","journal":null,"year":null,"id":654533,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":343353,"name":"Ellen Baxter","orcid":null,"position":1,"is_corresponding":false},{"id":718281,"name":"Mark Van Doren","orcid":"0000-0002-5475-003X","position":2,"is_corresponding":false},{"id":753058,"name":"Raghav Goyal","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>sisterless A</i>\n                  is required for activation of\n                  <i>Sex lethal</i>\n                  in the\n                  <i>Drosophila</i>\n                  germline","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Both somatic cells and germ cells must establish their correct sexual identity for proper gametogenesis. In\n                  <jats:italic>Drosophila,</jats:italic>\n                  sex determination in somatic cells is controlled by the switch gene\n                  <jats:italic>Sex lethal</jats:italic>\n                  (\n                  <jats:italic>Sxl</jats:italic>\n                  ), which is activated in females by the presence of two X chromosomes. Though germline sex determination is much less well understood,\n                  <jats:italic>Sxl</jats:italic>\n                  is also essential for the female identity in germ cells. Loss of\n                  <jats:italic>Sxl</jats:italic>\n                  function in the germline results in ovarian germline tumors, a characteristic of male germ cells developing in a female soma. Further,\n                  <jats:italic>Sxl</jats:italic>\n                  expression is sufficient for XY (male) germ cells to produce eggs when transplanted into XX (female) somatic gonads. As in the soma, the presence of two X chromosomes activates\n                  <jats:italic>Sxl</jats:italic>\n                  in the germline, but the mechanism for “counting” X chromosomes in the germline is thought to be different from the soma. Here we have explored this mechanism at both\n                  <jats:italic>cis</jats:italic>\n                  - and\n                  <jats:italic>trans-</jats:italic>\n                  levels. Our data support the model that the\n                  <jats:italic>Sxl</jats:italic>\n                  “establishment” promoter (\n                  <jats:italic>SxlPE</jats:italic>\n                  ) is activated in a female-specific manner in the germline, as in the soma, but that the timing of\n                  <jats:italic>SxlPE</jats:italic>\n                  activation, and the DNA elements that regulate\n                  <jats:italic>SxlPE,</jats:italic>\n                  are different in the germline. Nevertheless, we find that the X chromosome gene\n                  <jats:italic>sisterless A (sisA),</jats:italic>\n                  which helps activate\n                  <jats:italic>Sxl</jats:italic>\n                  in the soma, is also essential for\n                  <jats:italic>Sxl</jats:italic>\n                  activation in the germline. Loss of\n                  <jats:italic>sisA</jats:italic>\n                  leads causes of Sxl expression in the germline, and to ovarian tumors and germline loss. These defects can be rescued by Sxl expression, demonstrating that\n                  <jats:italic>sisA</jats:italic>\n                  lies upstream of\n                  <jats:italic>Sxl</jats:italic>\n                  in germline sex determination. We conclude that\n                  <jats:italic>sisA</jats:italic>\n                  acts as an X chromosome counting element in both the soma and the germline, but that additional factors regulating female-specific expression of\n                  <jats:italic>Sxl</jats:italic>\n                  in the germline remain to be discovered.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>AUTHOR SUMMARY</jats:title>\n                  <jats:p>\n                    The production of sperm and eggs requires proper sexual identity to be established in both somatic cells and the germ cells, which ultimately produce the gametes. While somatic sex determination has been well studied in a number of organisms, how germ cells establish their sexual identity is much less well understood. In Drosophila, the RNA binding protein Sex lethal (Sxl) is essential for female sexual identity in both the soma and the germline, but its regulation in the germline is thought to be different than in the soma. Here we explore how\n                    <jats:italic>Sxl</jats:italic>\n                    is activated in the germline. We find that the germline uses a different set of DNA elements to control activation of the key sex-specific\n                    <jats:italic>Sxl</jats:italic>\n                    promoter. Nonetheless, one of the activators of\n                    <jats:italic>Sxl</jats:italic>\n                    in the soma, the transcription factor Sisterless A (SisA), also acts to activate\n                    <jats:italic>Sxl</jats:italic>\n                    in the germline. Our data indicate that, while SisA acts as a common activator in both the soma and germline, additional, germline-specific\n                    <jats:italic>Sxl</jats:italic>\n                    activators remain to be discovered.\n                  </jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19965766","pmcid":null,"openalex_id":"https://openalex.org/W2995512452","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/01/02/2019.12.17.880070.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/01/02/2019.12.17.880070.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2019.12.17.880070","host_type":"publisher"},{"url":"https://doi.org/10.1101/2019.12.17.880070","host_type":"repository"}],"fields_of_study":["Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","Animal Behavior and Reproduction","Developmental Biology and Gene Regulation"],"mesh_terms":[],"keywords":["Germline","Soma","Somatic cell","Biology","Genetics","Germline mutation","Gene","Mutation","Neuroscience"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Gender equality"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T07:09:16.425682Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}