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000292522 1001_ $$aMonastirioti, Maria$$b0
000292522 245__ $$aNotch-Dependent Expression of the Drosophila Hey Gene Is Supported by a Pair of Enhancers with Overlapping Activities.
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000292522 520__ $$aDrosophila Hey is a basic helix-loop-helix-orange (bHLH-O) protein with an important role in the establishment of distinct identities of postmitotic cells. We have previously identified Hey as a transcriptional target and effector of Notch signalling during the asymmetric division of neuronal progenitors, generating neurons of two types, and we have shown that Notch-dependent expression of Hey also marks a subpopulation of the newborn enteroendocrine (EE) cells in the midgut primordium of the embryo. Here, we investigate the transcriptional regulation of Hey in neuronal and intestinal tissues. We isolated two genomic regions upstream of the promoter (HeyUP) and in the second intron (HeyIN2) of the Hey gene, based on the presence of binding motifs for Su(H), the transcription factor that mediates Notch activity. We found that both regions can direct the overlapping expression patterns of reporter transgenes recapitulating endogenous Hey expression. Moreover, we showed that while HeyIN2 represents a Notch-dependent enhancer, HeyUP confers both Notch-dependent and independent transcriptional regulation. We induced mutations that removed the Su(H) binding motifs in either region and then studied the enhancer functionality in the respective Hey mutant lines. Our results provide direct evidence that although both enhancers support Notch-dependent regulation of the Hey gene, their role is redundant, as a Hey loss-of-function lethal phenotype is observed only after deletion of all their Su(H) binding motifs by CRISPR/Cas9.
000292522 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000292522 650_7 $$2Other$$aDrosophila
000292522 650_7 $$2Other$$aHey
000292522 650_7 $$2Other$$aNotch
000292522 650_7 $$2Other$$aSu(H) binding site
000292522 650_7 $$2Other$$abasic helix–loop–helix–orange
000292522 650_7 $$2Other$$acentral nervous system
000292522 650_7 $$2Other$$aenhancer
000292522 650_7 $$2Other$$amidgut
000292522 650_7 $$2NLM Chemicals$$aDrosophila Proteins
000292522 650_7 $$2NLM Chemicals$$aBasic Helix-Loop-Helix Transcription Factors
000292522 650_7 $$2NLM Chemicals$$aReceptors, Notch
000292522 650_7 $$2NLM Chemicals$$aN protein, Drosophila
000292522 650_7 $$2NLM Chemicals$$aRepressor Proteins
000292522 650_7 $$2NLM Chemicals$$aSu(H) protein, Drosophila
000292522 650_2 $$2MeSH$$aAnimals
000292522 650_2 $$2MeSH$$aDrosophila Proteins: genetics
000292522 650_2 $$2MeSH$$aDrosophila Proteins: metabolism
000292522 650_2 $$2MeSH$$aBasic Helix-Loop-Helix Transcription Factors: genetics
000292522 650_2 $$2MeSH$$aBasic Helix-Loop-Helix Transcription Factors: metabolism
000292522 650_2 $$2MeSH$$aReceptors, Notch: genetics
000292522 650_2 $$2MeSH$$aReceptors, Notch: metabolism
000292522 650_2 $$2MeSH$$aGene Expression Regulation, Developmental
000292522 650_2 $$2MeSH$$aEnhancer Elements, Genetic
000292522 650_2 $$2MeSH$$aDrosophila melanogaster: genetics
000292522 650_2 $$2MeSH$$aRepressor Proteins: genetics
000292522 650_2 $$2MeSH$$aRepressor Proteins: metabolism
000292522 650_2 $$2MeSH$$aPromoter Regions, Genetic
000292522 650_2 $$2MeSH$$aSignal Transduction: genetics
000292522 7001_ $$0P:(DE-He78)b2c36a9237b50f6e89390cb22a073910$$aKoltsaki, Ioanna$$b1$$udkfz
000292522 7001_ $$00000-0003-3408-0371$$aPitsidianaki, Ioanna$$b2
000292522 7001_ $$00000-0002-1671-5487$$aSkafida, Emilia$$b3
000292522 7001_ $$aBatsiotos, Nikolaos$$b4
000292522 7001_ $$00000-0003-3912-701X$$aDelidakis, Christos$$b5
000292522 773__ $$0PERI:(DE-600)2527218-4$$a10.3390/genes15081071$$gVol. 15, no. 8, p. 1071 -$$n8$$p1071$$tGenes$$v15$$x2073-4425$$y2024
000292522 8564_ $$uhttps://inrepo02.dkfz.de/record/292522/files/genes-15-01071-v2.pdf
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