001     292522
005     20241031134100.0
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082 _ _ |a 570
100 1 _ |a Monastirioti, Maria
|b 0
245 _ _ |a Notch-Dependent Expression of the Drosophila Hey Gene Is Supported by a Pair of Enhancers with Overlapping Activities.
260 _ _ |a Basel
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520 _ _ |a Drosophila 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.
536 _ _ |a 311 - Zellbiologie und Tumorbiologie (POF4-311)
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650 _ 7 |a Drosophila
|2 Other
650 _ 7 |a Hey
|2 Other
650 _ 7 |a Notch
|2 Other
650 _ 7 |a Su(H) binding site
|2 Other
650 _ 7 |a basic helix–loop–helix–orange
|2 Other
650 _ 7 |a central nervous system
|2 Other
650 _ 7 |a enhancer
|2 Other
650 _ 7 |a midgut
|2 Other
650 _ 7 |a Drosophila Proteins
|2 NLM Chemicals
650 _ 7 |a Basic Helix-Loop-Helix Transcription Factors
|2 NLM Chemicals
650 _ 7 |a Receptors, Notch
|2 NLM Chemicals
650 _ 7 |a N protein, Drosophila
|2 NLM Chemicals
650 _ 7 |a Repressor Proteins
|2 NLM Chemicals
650 _ 7 |a Su(H) protein, Drosophila
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Drosophila Proteins: genetics
|2 MeSH
650 _ 2 |a Drosophila Proteins: metabolism
|2 MeSH
650 _ 2 |a Basic Helix-Loop-Helix Transcription Factors: genetics
|2 MeSH
650 _ 2 |a Basic Helix-Loop-Helix Transcription Factors: metabolism
|2 MeSH
650 _ 2 |a Receptors, Notch: genetics
|2 MeSH
650 _ 2 |a Receptors, Notch: metabolism
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Developmental
|2 MeSH
650 _ 2 |a Enhancer Elements, Genetic
|2 MeSH
650 _ 2 |a Drosophila melanogaster: genetics
|2 MeSH
650 _ 2 |a Repressor Proteins: genetics
|2 MeSH
650 _ 2 |a Repressor Proteins: metabolism
|2 MeSH
650 _ 2 |a Promoter Regions, Genetic
|2 MeSH
650 _ 2 |a Signal Transduction: genetics
|2 MeSH
700 1 _ |a Koltsaki, Ioanna
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700 1 _ |a Pitsidianaki, Ioanna
|0 0000-0003-3408-0371
|b 2
700 1 _ |a Skafida, Emilia
|0 0000-0002-1671-5487
|b 3
700 1 _ |a Batsiotos, Nikolaos
|b 4
700 1 _ |a Delidakis, Christos
|0 0000-0003-3912-701X
|b 5
773 _ _ |a 10.3390/genes15081071
|g Vol. 15, no. 8, p. 1071 -
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|t Genes
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|x 2073-4425
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