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Brinker levels regulated by a promoter proximal element support germ cell homeostasis

Dunipace, Leslie and Newcomb, Susan and Stathopoulos, Angelike (2022) Brinker levels regulated by a promoter proximal element support germ cell homeostasis. Development, 149 (3). Art. No. dev199890. ISSN 0950-1991. PMCID PMC8918798. doi:10.1242/dev.199890.

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A limited BMP signaling range in the stem cell niche of the ovary protects against germ cell tumors and promotes germ cell homeostasis. The canonical repressor of BMP signaling in both the Drosophila embryo and wing disc is the transcription factor Brinker (Brk), yet the expression and potential role of Brk in the germarium has not previously been described. Here, we find that brk expression requires a promoter-proximal element (PPE) to support long-distance enhancer action as well as to drive expression in the germarium. Furthermore, PPE subdomains have different activities; in particular, the proximal portion acts as a damper to regulate brk levels precisely. Using PPE mutants as well as tissue-specific RNA interference and overexpression, we show that altering brk expression within either the soma or the germline affects germ cell homeostasis. Remarkably, we find that Decapentaplegic (Dpp), the main BMP ligand and canonical antagonist of Brk, is upregulated by Brk in the escort cells of the germarium, demonstrating that Brk can positively regulate this pathway.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Dunipace, Leslie0000-0002-1739-6537
Newcomb, Susan0000-0002-8563-9422
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2022. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received 10 June 2021; Accepted 22 December 2021. We thank Gerard Campbel, Dorothea Godt and George Pyrowolakis for sharing fly stocks and antibodies, and Peiwei Chen for comments on the manuscript. Author contributions: Conceptualization: L.D., A.S.; Validation: L.D., S.N.; Formal analysis: L.D., S.N.; Investigation: L.D., S.N.; Resources: A.S.; Data curation: L.D., S.N.; Writing - original draft: L.D., S.N.; Writing - review & editing: L.D., S.N., A.S.; Visualization: L.D., S.N.; Supervision: A.S.; Project administration: A.S. This study was supported by funding from a National Institutes of Health grant (R03HD101961 to A.S.) and an American Cancer Society Postdoctoral Fellowship (PF-20-122-01 to S.N.). Open Access funding provided by the California Institute of Technology. Deposited in PMC for immediate release. Peer review history: The peer review history is available online at The authors declare no competing or financial interests.
Funding AgencyGrant Number
American Cancer SocietyPF-20-122-01
Subject Keywords:brinker, Promoter-proximal element, BMP signaling, Oogenesis, Niche, Germline stem cells, Undifferentiated germ cells, Drosophila melanogaster
Issue or Number:3
PubMed Central ID:PMC8918798
Record Number:CaltechAUTHORS:20220202-833768400
Persistent URL:
Official Citation:Leslie Dunipace, Susan Newcomb, Angelike Stathopoulos; brinker levels regulated by a promoter proximal element support germ cell homeostasis. Development 1 February 2022; 149 (3): dev199890. doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113214
Deposited By: Tony Diaz
Deposited On:02 Feb 2022 17:07
Last Modified:04 Apr 2022 16:53

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