Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development
<b>Background:</b> General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in <i>Drosophila</i>. Gcn5 contains a P300/CBP-associat...
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2024-12-01
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| author | Youfeng Li Yue Xu Ruike Li Sirui Huang Qiong Wu Jing Yan Zhigang Jiang Xiushan Wu Fang Li Yuequn Wang Yongqing Li Xiongwei Fan Wuzhou Yuan |
| author_facet | Youfeng Li Yue Xu Ruike Li Sirui Huang Qiong Wu Jing Yan Zhigang Jiang Xiushan Wu Fang Li Yuequn Wang Yongqing Li Xiongwei Fan Wuzhou Yuan |
| author_sort | Youfeng Li |
| collection | DOAJ |
| description | <b>Background:</b> General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in <i>Drosophila</i>. Gcn5 contains a P300/CBP-associated factor (PCAF) domain, a Gcn5-N-acetyltransferase (GNAT) domain, and a Bromodomain, allowing it to regulate gene expression through the acetylation of both histone and non-histone proteins. In <i>Drosophila</i>, Gcn5 is crucial for embryonic development, with maternal Gcn5 supporting early development. However, the functional mechanisms of Gcn5 after the depletion of maternal deposits remain unclear. <b>Methods:</b> Our study employed the Gal4/UAS-RNAi system to achieve whole-body or heart-specific <i>Gcn5</i> knockdown in <i>Drosophila</i> and selected 96-hour-old surviving larvae for transcriptomic and metabolomic analyses. <b>Results:</b> Omics results revealed that Gcn5 knockdown significantly impacts various metabolic pathways, as well as lysosomes, non-homologous end-joining, Toll and Imd signaling pathways, and circadian rhythms, among others. Furthermore, defects in chitin synthesis may be associated with impaired pupation. Additionally, heart-specific <i>Gcn5</i> knockdown affected cardiac physiology but appeared to have a potential protective effect against age-related cardiac decline. <b>Conclusions:</b> These findings deepen our understanding of Gcn5’s roles in <i>Drosophila</i> development and provide valuable insights for developing Gcn5-targeted therapies, particularly considering its involvement in various human diseases. |
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| institution | Kabale University |
| issn | 2218-1989 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj-art-8dbd8db7f4504b75b4ec18433a917a3b2024-12-27T14:39:33ZengMDPI AGMetabolites2218-19892024-12-01141268010.3390/metabo14120680Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> DevelopmentYoufeng Li0Yue Xu1Ruike Li2Sirui Huang3Qiong Wu4Jing Yan5Zhigang Jiang6Xiushan Wu7Fang Li8Yuequn Wang9Yongqing Li10Xiongwei Fan11Wuzhou Yuan12The Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, ChinaThe Laboratory of Heart Development Research, College of Life Science, Hunan Normal University, Changsha 410081, China<b>Background:</b> General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in <i>Drosophila</i>. Gcn5 contains a P300/CBP-associated factor (PCAF) domain, a Gcn5-N-acetyltransferase (GNAT) domain, and a Bromodomain, allowing it to regulate gene expression through the acetylation of both histone and non-histone proteins. In <i>Drosophila</i>, Gcn5 is crucial for embryonic development, with maternal Gcn5 supporting early development. However, the functional mechanisms of Gcn5 after the depletion of maternal deposits remain unclear. <b>Methods:</b> Our study employed the Gal4/UAS-RNAi system to achieve whole-body or heart-specific <i>Gcn5</i> knockdown in <i>Drosophila</i> and selected 96-hour-old surviving larvae for transcriptomic and metabolomic analyses. <b>Results:</b> Omics results revealed that Gcn5 knockdown significantly impacts various metabolic pathways, as well as lysosomes, non-homologous end-joining, Toll and Imd signaling pathways, and circadian rhythms, among others. Furthermore, defects in chitin synthesis may be associated with impaired pupation. Additionally, heart-specific <i>Gcn5</i> knockdown affected cardiac physiology but appeared to have a potential protective effect against age-related cardiac decline. <b>Conclusions:</b> These findings deepen our understanding of Gcn5’s roles in <i>Drosophila</i> development and provide valuable insights for developing Gcn5-targeted therapies, particularly considering its involvement in various human diseases.https://www.mdpi.com/2218-1989/14/12/680Gcn5knockdowntranscriptomemetabolome<i>Drosophila</i>pupation |
| spellingShingle | Youfeng Li Yue Xu Ruike Li Sirui Huang Qiong Wu Jing Yan Zhigang Jiang Xiushan Wu Fang Li Yuequn Wang Yongqing Li Xiongwei Fan Wuzhou Yuan Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development Metabolites Gcn5 knockdown transcriptome metabolome <i>Drosophila</i> pupation |
| title | Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development |
| title_full | Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development |
| title_fullStr | Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development |
| title_full_unstemmed | Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development |
| title_short | Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in <i>Drosophila</i> Development |
| title_sort | transcriptomic and metabolomic analysis reveals multifaceted impact of gcn5 knockdown in i drosophila i development |
| topic | Gcn5 knockdown transcriptome metabolome <i>Drosophila</i> pupation |
| url | https://www.mdpi.com/2218-1989/14/12/680 |
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