Summary
Brother and Big brother were isolated as Runt-interacting proteins and are homologous to CBF(beta), which interacts with the mammalian CBF(alpha) Runt-domain proteins. In vitro experiments indicate that Brother family proteins regulate the DNA binding activity of Runt-domain proteins without contacting DNA. In both mouse and human there is genetic evidence that the CBF(alpha) and CBF(beta) proteins function together in hematopoiesis and leukemogenesis. Here we demonstrate functional interactions between Brother proteins and Runt domain proteins in Drosophila. First, we show that a specific point mutation in Runt that disrupts interaction with Brother proteins but does not affect DNA binding activity is dysfunctional in several in vivo assays. Interestingly, this mutant protein acts dominantly to interfere with the Runt-dependent activation of Sxl-lethal transcription. To investigate further the requirements for Brother proteins in Drosophila development, we examine the effects of expression of a Brother fusion protein homologous to the dominant negative CBF(beta)::SMMHC fusion protein that is associated with leukemia in humans. This Bro::SMMHC fusion protein interferes with the activity of Runt and a second Runt domain protein, Lozenge. Moreover, we find that the effects of lozenge mutations on eye development are suppressed by expression of wild-type Brother proteins, suggesting that Brother/Big brother dosage is limiting in this developmental context. Results obtained when Runt is expressed in developing eye discs further support this hypothesis. Our results firmly establish the importance of the Brother and Big brother proteins for the biological activities of Runt and Lozenge, and further suggest that Brother protein function is not restricted to enhancing DNA-binding.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
An interview with Swathi Arur
Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.
Jim Wells and Hanna Mikkola join our team of Editors
We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.
New funding scheme supports sustainable events
As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.
Read & Publish participation continues to grow
“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”
Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.
Upcoming special issues
Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021
The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022
Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.
Development presents...
Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.
Save your spot at our next session:
10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit
Join our mailing list to receive news and updates on the series.