Maternal role of the histone methyltransferase trr in early embryo development of Drosophila melanogaster

Medientyp: E-Book

Titel: Maternal role of the histone methyltransferase trr in early embryo development of Drosophila melanogaster

Beteiligte: Schulte-Sasse, Mariana [Verfasser]; Iovino, Nicola [Sonstige]; Iovino, Nicola [Akademischer Betreuer]; Pyrowolakis, George [GutachterIn]; Claßen, Anne-Kathrin [GutachterIn]

Körperschaft: Albert-Ludwigs-Universität Freiburg, Fakultät für Biologie ; Max-Planck-Institut für Immunbiologie und Epigenetik ; International Max Planck Research School IMPRS ; Albert-Ludwigs-Universität Freiburg, Fakultät für Biologie ; Professur für Entwicklungsbiologie der Tiere

Erschienen: Freiburg: Universität, 2022

Umfang: Online-Ressource

Sprache: Englisch

DOI: 10.6094/UNIFR/227277

Identifikator:

Schlagwörter: Taufliege ; Embryonalentwicklung ; Chromatin ; Epigenetik ; Methyltransferasen ; Chromatinremodellierung ; Fruchtfliegen ; Eizelle ; Biochemie ; Stoffwechsel ; (local)doctoralThesis

Entstehung:

Hochschulschrift: Dissertation, Universität Freiburg, 2022

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Beschreibung: Abstract: The trithorax-related protein (trr) is the core histone-methyltransferase of a complex present in Drosophila melanogaster called COMPASS (complex of proteins associated with Set1) -like complex. trr contains a Set domain, which catalyzes the monomethylation of lysine 4 in histone 3 (H3K4me1), a mark that has been associated with enhancers and active transcription. In this project, we found that the maternal knockdown (KD) of trr in late oogenesis prevents pronuclear fusion of the parental genomes in fertilized embryos leading to full infertility of the flies. This phenotype is characterized by the retention of protamines on the sperm DNA, arrest of mitotic divisions, and development impairment at very early time points after fertilization. A combination of fly genetics, proteomics, biochemical and genomic approaches were used to dissect the molecular mechanisms underlying the maternal role of trr in early embryo development. We observed that the transcription of more than 200 genes is affected upon maternal depletion of trr independently of its methyltransferase catalytic activity. Individual knockdown of those identified trr-target genes is not enough to recapitulate the abovementioned early development phenotype. Therefore, the observed defects may have a polygenic origin and are thus the result of a systemic imbalance. Our metabolomics analysis indicates that indeed metabolite populations from central carbon pathways such as the tricarboxylic acid (TCA) cycle are strongly affected in eggs and embryos lacking maternal trr. Furthermore, partially hydrolyzed lipid species such as lysophosphatidylcholines accumulate in TrrKD embryos, thus suggesting that early embryo lipid metabolism is also affected. Interestingly, some of our identified trr-targets have functions related to lipid and carbon metabolism. These observations are relevant since early embryogenesis is a fast-paced process with very high energy demands. Hence, we propose that maternal trr regulates the transcription of genes that are essential in metabolic processes occurring during very early embryonic development. Additionally, a high number of new putative trr-interaction partners were detected in nuclear soluble fractions of the maternal germline. While already-known interaction partners seem to participate in transcriptional regulation of trr-targets, some of the new candidates are associated with structural components of the cell, such as the centrosome or the meiotic spindle, suggesting that trr might have additional roles beyond transcriptional regulation. Finally, we found that while trr and the nuclear ecdysone receptor (EcR) do not seem to interact in solution, there is a major overlap in their genomic binding sites, thus confirming previous reports that have proposed trr as a co-activator of EcR. Interestingly, preliminary data analysis suggests that there is no co-dependence in chromatin binding between EcR and trr. Even though EcR seems to participate in the transcriptional regulation of a subgroup of trr-targets, its absence in the maternal germline does not result in the early embryonic phenotype we observe upon depletion of trr. Therefore, we hypothesize that trr has also an EcR-independent role. This highlights its important place as part of a complex network of interactions that finely regulates transcription in the maternal germline of the fly

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