The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype

Gene regulation is important during tissue formation, but redundant systems make it difficult to study in vivo. The protein Jazf-1 is a member of the NuA4/TIP60 histone-modifying complex, and a transcriptional repressor has been suggested to be important for Drosophila melanogaster eye development....

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Main Authors: Stonbraker Madison P., DePaul Dominic A., Heidel-Roberts Ethan C., Greene Hallee, Johnson Matthew Logan
Format: Article
Language:English
Published: De Gruyter 2025-08-01
Series:Open Life Sciences
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Online Access:https://doi.org/10.1515/biol-2025-1164
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author Stonbraker Madison P.
DePaul Dominic A.
Heidel-Roberts Ethan C.
Greene Hallee
Johnson Matthew Logan
author_facet Stonbraker Madison P.
DePaul Dominic A.
Heidel-Roberts Ethan C.
Greene Hallee
Johnson Matthew Logan
author_sort Stonbraker Madison P.
collection DOAJ
description Gene regulation is important during tissue formation, but redundant systems make it difficult to study in vivo. The protein Jazf-1 is a member of the NuA4/TIP60 histone-modifying complex, and a transcriptional repressor has been suggested to be important for Drosophila melanogaster eye development. We used the GAL4-UAS system to determine the impact of altering gene expression. GAL4-UAS manipulations of Jazf-1 in the eye caused variable and not fully penetrant phenotypes. Increased expression of Jazf-1 has been shown to suppress a Lobe 2 small eye phenotype. We found that Lobe 2 produces a sensitive background for an in vivo assay to monitor gene regulatory complexes. Depleting Jazf-1 and other NuA4/TIP60 complex members significantly enhanced the eye phenotype. We also tested Hr78, which directly interacts with Jazf-1, and found it inversely modifies the Lobe 2 phenotype. An Hr78 mutation predicted to uncouple the Jazf-1 interaction but still capable of interactions with transcriptional activators further enhanced the Lobe 2 mutant phenotype, suggesting the loss of a repressing complex. We believe that Hr78 is acting as an anchor for repressing and activating complexes and the NuA4/TIP60 complex helps repress genes that can negatively impact eye formation in the context of Lobe 2.
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spelling doaj-art-0fe9f4da50344b378bc0e0567d3001242025-08-25T06:10:05ZengDe GruyterOpen Life Sciences2391-54122025-08-012016384510.1515/biol-2025-1164The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotypeStonbraker Madison P.0DePaul Dominic A.1Heidel-Roberts Ethan C.2Greene Hallee3Johnson Matthew Logan4Biology Department, University of Pittsburg at Greensburg, Greensburg, Pennsylvania, United States of AmericaBiology Department, University of Pittsburg at Greensburg, Greensburg, Pennsylvania, United States of AmericaBiology Department, University of Pittsburg at Greensburg, Greensburg, Pennsylvania, United States of AmericaBiology Department, University of Pittsburg at Greensburg, Greensburg, Pennsylvania, United States of AmericaBiology Department, University of Pittsburg at Greensburg, Greensburg, Pennsylvania, United States of AmericaGene regulation is important during tissue formation, but redundant systems make it difficult to study in vivo. The protein Jazf-1 is a member of the NuA4/TIP60 histone-modifying complex, and a transcriptional repressor has been suggested to be important for Drosophila melanogaster eye development. We used the GAL4-UAS system to determine the impact of altering gene expression. GAL4-UAS manipulations of Jazf-1 in the eye caused variable and not fully penetrant phenotypes. Increased expression of Jazf-1 has been shown to suppress a Lobe 2 small eye phenotype. We found that Lobe 2 produces a sensitive background for an in vivo assay to monitor gene regulatory complexes. Depleting Jazf-1 and other NuA4/TIP60 complex members significantly enhanced the eye phenotype. We also tested Hr78, which directly interacts with Jazf-1, and found it inversely modifies the Lobe 2 phenotype. An Hr78 mutation predicted to uncouple the Jazf-1 interaction but still capable of interactions with transcriptional activators further enhanced the Lobe 2 mutant phenotype, suggesting the loss of a repressing complex. We believe that Hr78 is acting as an anchor for repressing and activating complexes and the NuA4/TIP60 complex helps repress genes that can negatively impact eye formation in the context of Lobe 2.https://doi.org/10.1515/biol-2025-1164gal4/uasjazf-1hr78enhancersuppressor
spellingShingle Stonbraker Madison P.
DePaul Dominic A.
Heidel-Roberts Ethan C.
Greene Hallee
Johnson Matthew Logan
The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
Open Life Sciences
gal4/uas
jazf-1
hr78
enhancer
suppressor
title The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
title_full The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
title_fullStr The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
title_full_unstemmed The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
title_short The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
title_sort nua4 tip60 histone modifying complex and hr78 modulate the lobe2 mutant eye phenotype
topic gal4/uas
jazf-1
hr78
enhancer
suppressor
url https://doi.org/10.1515/biol-2025-1164
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