Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development
Highly evolutionarily conserved multiprotein complexes termed Complex of Proteins Associated with Set1 (COMPASS) are required for histone 3 lysine 4 (H3K4) methylation. <i>Drosophila</i> Set1, Trx, and Trr form the core subunits of these complexes. We show that flies deficient in any of...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17314 |
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| author | Jun-yi Zhu Hangnoh Lee Xiaohu Huang Joyce van de Leemput Zhe Han |
| author_facet | Jun-yi Zhu Hangnoh Lee Xiaohu Huang Joyce van de Leemput Zhe Han |
| author_sort | Jun-yi Zhu |
| collection | DOAJ |
| description | Highly evolutionarily conserved multiprotein complexes termed Complex of Proteins Associated with Set1 (COMPASS) are required for histone 3 lysine 4 (H3K4) methylation. <i>Drosophila</i> Set1, Trx, and Trr form the core subunits of these complexes. We show that flies deficient in any of these three subunits demonstrated high lethality at eclosion (emergence of adult flies from their pupal cases) and significantly shortened lifespans for the adults that did emerge. Silencing <i>Set1</i>, <i>trx</i>, or <i>trr</i> in the heart led to a reduction in H3K4 monomethylation (H3K4me1) and dimethylation (H3K4me2), reflecting their distinct roles in H3K4 methylation. Furthermore, we studied the gene expression patterns regulated by Set1, Trx, and Trr. Each of the COMPASS core subunits controls the methylation of different sets of genes, with many metabolic pathways active early in development and throughout, while muscle and heart differentiation processes were methylated during later stages of development. Taken together, our findings demonstrate the roles of COMPASS series complex core subunits Set1, Trx, and Trr in regulating histone methylation during heart development and, given their implication in congenital heart diseases, inform research on heart disease. |
| first_indexed | 2024-03-08T20:42:02Z |
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| id | doaj.art-aa478b09e5d2472ea7ae5173892b9dbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:42:02Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa478b09e5d2472ea7ae5173892b9dbb2023-12-22T14:14:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241731410.3390/ijms242417314Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart DevelopmentJun-yi Zhu0Hangnoh Lee1Xiaohu Huang2Joyce van de Leemput3Zhe Han4Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USAHighly evolutionarily conserved multiprotein complexes termed Complex of Proteins Associated with Set1 (COMPASS) are required for histone 3 lysine 4 (H3K4) methylation. <i>Drosophila</i> Set1, Trx, and Trr form the core subunits of these complexes. We show that flies deficient in any of these three subunits demonstrated high lethality at eclosion (emergence of adult flies from their pupal cases) and significantly shortened lifespans for the adults that did emerge. Silencing <i>Set1</i>, <i>trx</i>, or <i>trr</i> in the heart led to a reduction in H3K4 monomethylation (H3K4me1) and dimethylation (H3K4me2), reflecting their distinct roles in H3K4 methylation. Furthermore, we studied the gene expression patterns regulated by Set1, Trx, and Trr. Each of the COMPASS core subunits controls the methylation of different sets of genes, with many metabolic pathways active early in development and throughout, while muscle and heart differentiation processes were methylated during later stages of development. Taken together, our findings demonstrate the roles of COMPASS series complex core subunits Set1, Trx, and Trr in regulating histone methylation during heart development and, given their implication in congenital heart diseases, inform research on heart disease.https://www.mdpi.com/1422-0067/24/24/17314heart developmenthistone modification<i>Drosophila</i><i>Set1</i><i>trx</i><i>trr</i> |
| spellingShingle | Jun-yi Zhu Hangnoh Lee Xiaohu Huang Joyce van de Leemput Zhe Han Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development International Journal of Molecular Sciences heart development histone modification <i>Drosophila</i> <i>Set1</i> <i>trx</i> <i>trr</i> |
| title | Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development |
| title_full | Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development |
| title_fullStr | Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development |
| title_full_unstemmed | Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development |
| title_short | Distinct Roles for COMPASS Core Subunits Set1, Trx, and Trr in the Epigenetic Regulation of <i>Drosophila</i> Heart Development |
| title_sort | distinct roles for compass core subunits set1 trx and trr in the epigenetic regulation of i drosophila i heart development |
| topic | heart development histone modification <i>Drosophila</i> <i>Set1</i> <i>trx</i> <i>trr</i> |
| url | https://www.mdpi.com/1422-0067/24/24/17314 |
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