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DamID profiling of neural transcription factor binding in Drosophila melanogaster embryos

ABSTRACT: Paper abstract: Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Amongst its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a short-cut to identifying genes important for nervous system development.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE18270 | GEO | 2009/09/25

SECONDARY ACCESSION(S): PRJNA117941

REPOSITORIES: GEO

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DamID profiling of neural transcription factor binding in Drosophila melanogaster embryos

Project description:Paper abstract: Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Amongst its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a short-cut to identifying genes important for nervous system development. Each Dam-fusion-derived sample is compared to a control Dam-only sample. Four biological replicates were performed for Prospero (with 2 dye-swaps). For Asense, Deadpan and Snail, two biological replicates were performed.

2010-05-22 | E-GEOD-18270 | biostudies-arrayexpress

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Project description:Paper abstract: Stem cells have the remarkable ability to give rise to both self-renewing and differentiating daughter cells. Drosophila neural stem cells segregate cell-fate determinants from the self-renewing cell to the differentiating daughter at each division. Here, we show that one such determinant, the homeodomain transcription factor Prospero, regulates the choice between stem cell self-renewal and differentiation. We have identified the in vivo targets of Prospero throughout the entire genome. We show that Prospero represses genes required for self-renewal, such as stem cell fate genes and cell-cycle genes. Surprisingly, Prospero is also required to activate genes for terminal differentiation. We further show that in the absence of Prospero, differentiating daughters revert to a stem cell-like fate: they express markers of self-renewal, exhibit increased proliferation, and fail to differentiate. These results define a blueprint for the transition from stem cell self-renewal to terminal differentiation. 6 wildtype samples and 6 prospero mutant samples were hybridised to arrays against a commom reference sample (generated from whole embryo cDNA). The prospero samples were indirectly compared to the wildtype samples via the common reference. Half the wildtype and half of the prospero arrays were dye-swapped.

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