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Brk regulates wing disc growth in part via repression of Myc expression.

ABSTRACT: The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signalling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth by repression of the transcription factor Brk. The transcriptional targets of Brk that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-Seq of endogenous Brk from wing imaginal discs. We identify the growth regulator Myc as a target of Brk and show that repression of Myc and of the miRNA bantam explains a significant fraction of the growth inhibition caused by Brk. This work sheds light on the effector mechanisms by which Dpp signalling controls tissue growth.

SUBMITTER: Doumpas N

PROVIDER: S-EPMC3589086 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Brk regulates wing disc growth in part via repression of Myc expression.

Doumpas Nikolaos N Ruiz-Romero Marina M Blanco Enrique E Edgar Bruce B Corominas Montserrat M Teleman Aurelio A AA

EMBO reports 20130122 3

The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signalling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth by repression of the transcription factor Brk. The transcriptional targets of Brk that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-Seq of endogenous Brk from wing imaginal discs. We identify the growth regulator Myc as a target of Brk a ...[more]

PMID: 23337628

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Brinker regulates wing disc growth in part via repression of Myc expression

Project description:The molecular mechanisms regulating tissue size represent an unsolved puzzle in developmental biology. One signaling pathway controlling growth of the Drosophila wing is Dpp. Dpp promotes growth via repression of the transcription factor Brinker. The transcriptional targets of Brinker that control cell growth and proliferation, however, are not yet fully elucidated. We report here a genome-wide ChIP-seq of endogenous Brinker from wing imaginal discs. We identify the growth regulator Myc as a target of Brinker and show that Myc together with the microRNA bantam explain a large fraction of the growth inhibition caused by Brinker. This work sheds light on the effector mechanisms by which Dpp signaling controls tissue growth. Identification of Brinker binding sites in Wing imaginal discs cells

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Target of Rapamycin Complex 2 regulates cell growth via Myc in Drosophila.

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Project description:Precise regulation of Rag (recombination-activating gene) expression is crucial to prevent genomic instability caused by the generation of Rag-mediated DNA breaks. Although mechanisms of Rag activation have been well characterized, the mechanism by which Rag expression is down-regulated in early B cell development has not been fully elucidated. Using a complementary DNA library screen, we identified the transcriptional repressor Gfi1b as negative regulator of the Rag locus. Expression of Gfi1b causes repression of Rag1 and Rag2 in cell lines and primary mouse cells. Conversely, Gfi1b-deficient cell lines exhibit increased Rag expression, double-strand breaks and recombination, and cell cycle defects. In primary cells, transcription of Gfi1b inversely correlates with Rag transcription, and simultaneous inactivation of Gfi1 and Gfi1b leads to an increase in Rag transcription early in B cell development. In addition, deletion of Gfi1 and Gfi1b in vivo results in a severe block in B cell development. Gfi1b orchestrates Rag repression via a dual mechanism. Direct binding of Gfi1b to a site 5' of the B cell-specific Erag enhancer results in epigenetic changes in the Rag locus, whereas indirect inhibition is achieved through repression of the trans-activator Foxo1. Together, our experiments show that Gfi family members are essential for normal B cell development and play an important role in modulating expression of the V(D)J recombinase.

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