SETDB1 modulates the differentiation of both the crystal cells and the lamellocytes in Drosophila
| Autor: | Dushyant Kumar Gautam, Indira Paddibhatla, Rakesh Mishra |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Hemocytes
Notch signaling pathway Epigenesis Genetic Blood cell 03 medical and health sciences 0302 clinical medicine medicine Animals Drosophila Proteins Epigenetics Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences biology Wild type Lamellocyte differentiation Cell Differentiation Cell Biology Histone-Lysine N-Methyltransferase biology.organism_classification Phenotype Cell biology Hematopoiesis Haematopoiesis medicine.anatomical_structure Drosophila melanogaster Larva 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Developmental biology. 456(1) |
| ISSN: | 1095-564X |
| Popis: | Proper genetic and epigenetic regulation is necessary to maintain the identity and integrity of cells. Enzymes involved in post-transcriptional modifications of histones are key factors in epigenetic mechanisms. Such modifications are also gaining importance for their role in growth and development of cancer. SETDB1 catalyzes the epigenetic mark of lysine-9 methylation of histone-3. In this study, we explored the role of SETDB1 in Drosophila hematopoiesis. We show that SETDB1 controls the differentiation of matured blood cells in wandering third instar larvae. There are three matured blood cells in wild type Drosophila melanogaster: plasmatocytes, crystal cells and lamellocytes. We found that loss-of-function mutants of SETDB1 show hematopoietic defects; increased blood cell proliferation, decreased number of crystal cells, greater differentiation of blood cells into lamellocytes, dysplasia of the anterior lobes of lymph gland and presence of hematopoietic tumors. Cell type specific knockdown of SETDB1 provided similar phenotype i.e., decreased number of crystal cells and an increase in lamellocyte differentiation. In animals with loss of function of SETDB1, Notch pathway was downregulated. Further, over-expression of SETDB1 in blood cells resulted in an increase in the number of crystal cells. This increase is accompanied with an increase in the number of NotchICD expressing cells. We therefore performed genetic rescue using UAS-GAL4 system to rescue loss of function SETDB1 mutants. Our data show that the rescued larvae carrying a wild type copy of SETDB1 in mutant background are devoid of blood tumors. We have identified a novel dual function of SETDB1 methylatransferase as a critical regulator of two of the matured hemocytes, crystal cells and lamellocytes. We propose a novel role of SETDB1 in modulating the differentiation of crystal cells and lamellocytes from a common progenitor and underscore the importance of SETDB1 in Drosophila blood tumor suppression. |
| Databáze: | OpenAIRE |
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