The<i>Drosophila</i>bZIP transcription factor Vrille is involved in hair and cell growth

Szuplewski, Sébastien; Kottler, Benjamin; Terracol, Régine

doi:10.1242/dev.00588

Cited by 21 publications

(28 citation statements)

References 115 publications

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“…OvoQ6 was specific to Svb targets since it was not detected in control epidermal genes (Figure S1C in Additional file 1). In contrast, motifs matching the BS of TFs involved in general epidermis differentiation, such as Grainy head [42] or Vrille/c-EBP [43], were highly ranked in Svb-independent genes (Figure S1C in Additional file 1) while lowly ranked in Svb downstream genes. Hence, OvoQ6 motifs appear to be a signature of a subset of genes activated by Svb, a result consistent with their direct regulation.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization

et al. 2013

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BackgroundDevelopmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.ResultsWe defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome cells. Coupling computational modeling to functional dissection, we investigated the regulatory logic of these enhancers. Extending the repertoire of epidermal effectors using genome-wide approaches showed that the regulatory models learned from this first sample are representative of the whole set of trichome enhancers. These enhancers harbor remarkable features with respect to their functional architectures, including a weak or non-existent clustering of Svb binding sites. The in vivo function of each site relies on its intimate context, notably the flanking nucleotides. Two additional cis-regulatory motifs, present in a broad diversity of composition and positioning among trichome enhancers, critically contribute to enhancer activity.ConclusionsOur results show that Svb directly regulates a large set of terminal effectors of the remodeling of epidermal cells. Further, these data reveal that trichome formation is underpinned by unexpectedly diverse modes of regulation, providing fresh insights into the functional architecture of enhancers governing a terminal differentiation program.

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Section: Resultsmentioning

confidence: 99%

Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization

et al. 2013

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“…vri clones in the adult cuticle contain smaller cells with atrophic bristles. Also, overexpression of Vrille is antiproliferative in embryonic dorsal epidermis, induces apoptosis in imaginal discs, and gives rise to smaller cells and organs in salivary glands (Szuplewski et al 2003 Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

Genomic mapping of binding regions for the Ecdysone receptor protein complex

Gauhar¹,

Sun²,

Hua³

et al. 2009

Genome Res.

115

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We determined the physical locations of the heterodimeric Ecdysone receptor/Ultraspiracle (ECR/USP) nuclear hormone receptor complex throughout the entire nonrepetitive genome of Drosophila melanogaster using a cell line (Kc167) that differentiates in response to 20-hydroxyecdysone (20-HE). 20-HE, the natural ligand of this complex, controls major aspects of insect development, including molting, metamorphosis, and reproduction. Direct gene targets of 20-HE signaling were identified by combining this physical binding-site profiling with gene expression profiling after treatment with 20-HE. We found 502 significant regions of ECR/USP binding throughout the genome. Only 42% of these regions are nearby genes that are 20-HE responsive in these cells. However, at least three quarters of the remaining ECR/USP regions are near 20-HE-regulated genes in other tissue and cell types during metamorphosis, suggesting that binding at many regulatory elements in the genome is largely noncell-type specific. The majority (21/26) of the early targets of 20-HE encode transcriptional regulatory factors. To determine whether any of these targets are required for the morphological differentiation of these cells, we used RNAi to reduce the expression of each of the 26 early genes. Accordingly, we found that three direct targets of ECR/USP-hairy, vrille, and Hr4 -are required for cellular differentiation in response to the hormone. Initial mutational analysis of vrille in vivo reveals that it is required for metamorphosis.

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“…Notably, while PAR containing bZIP factors activate transcription, E4BP4 represses transcription [12]. Other homologous PAR domain lacking bZIP genes include the C. elegans ces-2 (cell death selector) gene, which promotes neuronal cell death, the Drosophila vrille gene, which induces apoptosis in embryonic dorsal epidermis, and genes 8 and 9 in X. laevis, which contribute to tail resorption [13,14]. Based on these homologous genes, one might expect E4BP4 to be pro-apoptotic; however, depending of the cell type and downstream effectors, E4BP4 has been shown to promote cell survival [15,16], induce apoptosis [17], or promote parathyroid hormone-mediated catabolism in osteoblasts [11].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in rat motoneurons, E4BP4 serves as a survival factor, and is expressed at high levels in those neurons that escape natural apoptosis [16]. Interestingly, the C. elegans CES-2 blocks the activity of a survival factor, CES-1, to evoke an apoptotic response [13]. The vertebrate homolog of CES-1, Slug, is upregulated in leukemic B-lymphoblasts by the chimeric oncoprotein, E2A-HLF, which binds to the same consensus sequence as, and is proposed to act similarly to E4BP4 [35].…”

Section: Discussionmentioning

confidence: 99%

“…E4BP4 belongs to a highly conserved family of proteins involved in programmed cell death/cell proliferation [12]. Genes closely related to mammalian E4BP4 include genes 8 & 9 of Xaenopus laevis, ces-2 of Caenorhabditis elegans, and vrille of Drosophila melanogaster, all of which are involved in pro-apoptotic events such as tail resorption, neuronal cell death, and activation of pro-apoptotic signaling molecules [13,14]. In contrast to its evolutionarily conserved function as a promoter of cell death, E4BP4 has been suggested to protect growth factor-dependent B-lymphocytes from apoptosis caused by interleukin-3 deprivation [15].…”

mentioning

confidence: 99%

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Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells

Priceman

Kirzner

Nary

et al. 2006

Biochemical and Biophysical Research Communications

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Glucocorticoid (GC)-evoked apoptosis of T-lymphoid cells is preceded by increases in the intracellular Ca 2+ concentration ([Ca 2+ ] i ), which may contribute to apoptosis. This report demonstrates that GC-mediated upregulation of the bZIP transcriptional repressor gene, E4BP4, is dependent on [Ca 2+ ] i levels, and correlates with GC-evoked apoptosis of GC-sensitive CEM-C7-14 cells. Calcium chelators EGTA and BAPTA reduced [Ca 2+ ] i levels and protected CEM-C7-14 cells from Dex-evoked E4BP4 upregulation as well as apoptosis. In the GC-resistant sister clone, CEM-C1-15, Dex treatment did not induce [Ca 2+ ] i levels, E4BP4 expression or apoptosis, however, the calcium ionophore A23187 restored Dex-evoked E4BP4 upregulation and apoptosis. CEM-C7-14 cells were more sensitive to GC-independent increases in [Ca 2+ ] i levels by thapsigargin, and a corresponding increase in E4BP4 expression and cell death, compared to CEM-C1-15 cells, suggesting a direct correlation between [Ca 2+ ] i levels, E4BP4 expression, and apoptosis.

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TheDrosophilabZIP transcription factor Vrille is involved in hair and cell growth

Cited by 21 publications

References 115 publications

Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization

Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization

Genomic mapping of binding regions for the Ecdysone receptor protein complex

Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells

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