Project description:The histone demethylase LSD1 is a key chromatin regulator that plays a crucial role in development. It has been shown to act both as a co-repressor and a co-activator of genes expression and to affect the expression of many genes important for development. In Drosophila, dLsd1 is essential for oogenesis; however, our current knowledge of dLsd1 function is insufficient to explain its precise role in the ovary. To better define the role of dLsd1 in oogenesis, we performed genome-wide analysis of dLsd1 binding in the ovary by Chromatin Immunoprecipitation followed by sequencing (ChIP-Seq).
Project description:To study the effect of dLsd1 knockdown on gene expression in oogenesis, we performed transcripts profiling by microarray in wild type ovaries and ovaries depleted for dLsd1.
Project description:Determination of tissue size depends on the proper response of cells to a wide array of external and internal signals. Chromatin acts as a platform/substrate of signal integration and storage. Signal transduction pathways converge upon chromatin modifying enzymes and transcription factors to reprogram gene expression. However, little is known about the role of chromatin modifying factors in determining tissue size. Here, we show that loss of function of the histone demethylase dLSD1 results in a significant reduction of Drosophila wing size due to a decreased cell number. We show that dLSD1 depletion affects proliferation and induces DNA damage in larval wing imaginal discs. Through transcriptomics analysis, we find that dLSD1 controls the expression of multiple gene networks in wing imaginal discs. We then show that normal dLsd1 function contributes to repressing Transposable Element (TE) transcription and mobility. Additionally, our results suggest that increased TE mobility due to dLsd1 depletion contributes directly to altered organ size.
Project description:The specific role of chromatin modifying factors in the timely execution of transcriptional changes in gene expression to regulate organ size remains largely unknown. Here, we report that in Drosophila melanogaster depletion of the histone demethylase dLsd1 results in the reduction of wing size. dLsd1 depletion affects cell proliferation and causes an increase in DNA damage and cell death. Mechanistically, we have identified Transposable Elements (TEs) as critical dLsd1 targets for organ size determination. We found that upon dLsd1 loss many TE families are upregulated, and new TE insertions appear. By blocking this new TE activity, we could rescue the wing size phenotype. Collectively, our results reveal that the histone demethylase dLsd1 and maintenance of TE homeostasis are required to ensure proper wing size.
Project description:The histone demethylase LSD1 is a key chromatin regulator that is often deregulated in cancer. Its ortholog, dLsd1 plays a crucial role in Drosophila oogenesis; however, our knowledge of dLsd1 function is insufficient to explain its role in the ovary. Here, we have performed genome-wide analysis of dLsd1 binding in the ovary, and we document that dLsd1 is preferentially associated to the transcription start site of developmental genes. We uncovered an unanticipated interplay between dLsd1 and the GATA transcription factor Serpent and we report an unexpected role for Serpent in oogenesis. Besides, our transcriptomic data show that reducing dLsd1 levels results in ectopic transposable elements (TE) expression correlated with changes in H3K4me2 and H3K9me2 at TE loci. In addition, our results suggest that dLsd1 is required for Piwi dependent TE silencing. Hence, we propose that dLsd1 plays crucial roles in establishing specific gene expression programs and in repressing transposons during oogenesis.
Project description:This SuperSeries is composed of the following subset Series: GSE18588: CpG islands recruit a histone H3 lysine 36 demethylase [Illumina sequencing data] GSE21201: CpG islands recruit a histone H3 lysine 36 demethylase [Agilent data] Refer to individual Series