Details

Autor(en) / Beteiligte

• Crona, Filip
• Holmqvist, Per-Henrik
• Tang, Min
• Singla, Bhumica
• Vakifahmetoglu-Norberg, Helin
• Fantur, Katrin
• Mannervik, Mattias

Titel

The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos

Ist Teil von

• Developmental biology, 2015-11, Vol.407 (1), p.173-181

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• The Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is poorly understood. We previously showed that Brakeless can function as a transcriptional co-repressor. In this work, we perform transcriptional profiling of brakeless mutant embryos. Unexpectedly, the majority of affected genes are down-regulated in brakeless mutants. We demonstrate that genomic regions in close proximity to some of these genes are occupied by Brakeless, that over-expression of Brakeless causes a reciprocal effect on expression of these genes, and that Brakeless remains an activator of the genes upon fusion to an activation domain. Together, our results show that Brakeless can both repress and activate gene expression. A yeast two-hybrid screen identified the Mediator complex subunit Med19 as interacting with an evolutionarily conserved part of Brakeless. Both down- and up-regulated Brakeless target genes are also affected in Med19-depleted embryos, but only down-regulated targets are influenced in embryos depleted of both Brakeless and Med19. Our data provide support for a Brakeless activator function that regulates transcription by interacting with Med19. We conclude that the transcriptional co-regulator Brakeless can either activate or repress transcription depending on context. •Brakeless is a transcriptional co-regulator important for Drosophila development.•We show that Brakeless can both repress and activate transcription.•Brakeless interacts with the Mediator complex subunit Med19.•Brakeless co-activator function may involve its interaction with Med19.•Transcriptional co-regulators can switch activity depending on context.