Unknown,Transcriptomics,Genomics,Proteomics

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MORC1 represses transposable elements in the mouse male germ line

ABSTRACT: The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA methylated and silent genes. MORC1 deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homolog DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation. This data includes: 47 RNA-seq, 4 smRNA-seq, 6 BS-seq, and 2 ChIP-seq datasets

ORGANISM(S): Mus musculus

SUBMITTER: Hume Stroud

PROVIDER: E-GEOD-63048 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the relation between genome architecture and gene regulation in Plasmodium, we studied the genome structure of P. falciparum at three time points during its erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), we obtained high-resolution chromosomal contact maps, which we then used to construct a consensus three-dimensional genome structure for each time point. We observe strong clustering of centromeres, telomeres, ribosomal DNA and virulence genes, resulting in a complex architecture that cannot be explained by a simple volume exclusion model. Internal virulence gene clusters appear to be an important factor in shaping the genome architecture as they exhibit domain-like structures similar to topological domains in mammalian genomes. Midway during the cell cycle, at the highly transcriptionally active trophozoite stage, the genome adopts a more open chromatin structure with increased chromosomal intermingling. In addition, we observed reduced expression of genes located in spatial proximity to the repressive subtelomeric center, and colocalization of distinct groups of parasite-specific genes with coordinated expression profiles. Overall, our results are indicative of a strong association between the P. falciparum spatial genome organization and gene expression. Understanding the molecular processes involved in genome conformation dynamics could contribute to the discovery of novel antimalarial strategies. Analysis of the spatial organization of the P. falciparum genome at three stages of the erythrocytic cycle using chromosome conformation capture coupled with next generation sequencing (Hi-C). As a control, we included one sample for which chromatin contacts were not preserved by crosslinking of DNA and proteins.

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MORC1 represses transposable elements in the mouse male germ line

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