Ascaris suum
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ABSTRACT:
PROVIDER: PRJNA308932 | ENA |
REPOSITORIES: ENA
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Project description:The stability of the genome is paramount to organisms. However, diverse eukaryotes carry out programmed DNA elimination in which portions or entire chromsomes are lost in early development or during sex determination. During early development of the parasitic nematode, Ascaris suum, 13% of the genome is eliminated. How different genomic segments are reproducibly retained or discarded is unknown. Here, we show that centromeric histone CENP-A localization plays a key role in this process. We show that Ascaris chromosomes are holocentric during germline mitoses, with CENP-A distributed along their length. Prior to DNA elimination in the four-cell embryo, CENP-A is significantly diminished in chromosome regions that will be lost. This leads to the absence of kinetochores and microtubule attachment sites necessary for chromosome segregation, resulting in loss of these regions upon mitosis. Our data suggest that changes in CENP-A localization specify which portions of chromosomes will be lost during programmed DNA elimination.
2016-07-15 | GSE76914 | GEO
Project description:Comparative Genome Analysis of Programmed DNA Elimination in Nematodes (Ascaris)
| PRJNA388699 | ENA
Project description:Organisms invest significant effort into maintaining genome stability. However, in diverse groups of eukaryotes, portions or entire chromosomes are lost in early development or during sex determination, a process known as programmed DNA elimination. Little is known about how different segments of the genome are reproducibly retained and discarded during programmed DNA elimination. We tested the hypothesis that selective retention is mediated by regulation of centromere-mediated association of chromosome segments with the mitotic spindle. We report that on the holocentric chromosomes of the nematode Ascaris, the core centromeric histone CENP-A is localized differently in cells undergoing DNA elimination from those undergoing germline mitosis. Prior to DNA elimination, CENP-A is significantly reduced in chromosome regions that will be lost. CENP-A reduction in eliminated genomic regions leads to the absence of kinetochores and microtubule attachment sites necessary for chromosome segregation, and thus the loss of these DNA regions during Ascaris programmed DNA elimination. Our results show that holocentric chromosome organization in Ascaris is regulated and that changes in CENP-A deposition specify which portions of chromosomes will be eliminated during programmed DNA elimination. A total of 62 samples are analyzed. These include: (1). CENP-A ChIP-seq on 12 developmental stages with input and replicates (12 x 2 x 2 samples); (2). CENP-C ChIP-seq on 3 developmental stages with input and replicates (total 8 samples); and (3). Histone marks ChIP-seq with 6 samples
2016-07-15 | E-GEOD-76914 | biostudies-arrayexpress
Project description:Programmed DNA elimination is a developmentally regulated process leading to the reproducible loss of specific genomic sequences. DNA elimination occurs in unicellular ciliates and a variety of metazoans, including invertebrates and vertebrates. In metazoa, DNA elimination typically occurs in somatic cells during early development, leaving the germline genome intact. Reference genomes for metazoa that undergo DNA elimination are not available. Here, we generated germline and somatic reference genome sequences of the DNA eliminating pig parasitic nematode Ascaris suum and the horse parasite Parascaris univalens. In addition, we carried out in-depth analyses of DNA elimination in the parasitic nematode of humans, Ascaris lumbricoides, and the parasitic nematode of dogs, Toxocara canis. Our analysis of nematode DNA elimination reveals that in all species, repetitive sequences (that differ among the genera) and germline-expressed genes (approximately 1000-2000 or 5%-10% of the genes) are eliminated. Thirty-five percent of these eliminated genes are conserved among these nematodes, defining a core set of eliminated genes that are preferentially expressed during spermatogenesis. Our analysis supports the view that DNA elimination in nematodes silences germline-expressed genes. Over half of the chromosome break sites are conserved between Ascaris and Parascaris, whereas only 10% are conserved in the more divergent T. canis. Analysis of the chromosomal breakage regions suggests a sequence-independent mechanism for DNA breakage followed by telomere healing, with the formation of more accessible chromatin in the break regions prior to DNA elimination. Our genome assemblies and annotations also provide comprehensive resources for analysis of DNA elimination, parasitology research, and comparative nematode genome and epigenome studies.
2017-08-15 | GSE99523 | GEO
Project description:Restricting the localization of the centromeric histone H3 variant CENP-A to centromeres is essential to prevent chromosomal instability (CIN). Mislocalization of overexpressed CENP-A contributes to CIN in yeast, fly, and human cells. CENP-A is overexpressed in many cancers. Therefore, defining mechanisms that prevent CENP-A mislocalization will help us understand how CENP-A overexpression contributes to CIN in cancer. A genome-wide screen to characterize essential genes required for growth when CENP-A is overexpressed identified the replication initiation Dbf4-Dependent Kinase (DDK) complex. We show that DDK regulates ubiquitin-mediated proteolysis of Cse4 and prevents mislocalization of Cse4 independently of its role in DNA replication.
2020-04-04 | GSE148068 | GEO
Project description:Centromeric localization of the evolutionarily conserved histone H3 variant, CENP-A. is essential for chromosomal stability. CENP-A overexpression (OE) causesd its mislocalization to non-centromeric regions resulting in chromosomal instability (CIN) in yeast, flies and human cells. CENP-A OE and mislocalization have been observed in cancers and correlates with poor prognosis. However, the molecular consequences of CENP-A OE on CIN and aneuploidy have not been defined. Here, we overexpressed YFP-CENP-A in a pseudodiploid DLD1 cell line and showed that CENP-A OE leads to its mislocalization and CIN due to defects in kinetochore integrity and kinetochore-microtubule attachments. CENP-A OE also leads to its mislocalization and CIN in a xenograft mouse model. Under these conditions, it contributes to aneuploidy with karyotypic heterogeneity in human cells and xenograft mouse model. In summary, our studies provide a molecular link between CENP-A OE and aneuploidy, and suggest that karyotypic heterogeneity may contribute to the aggressive phenotype of CENP-A overexpressing cancers.
2020-07-16 | GSE154460 | GEO
Project description:The centromeric histone H3 variant CENP-A is overexpressed in many cancers. Mislocalization of CENP-A to non-centromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. Despite these observations, pathways that promote and prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen to identify regulators of CENP-A localization. We identified DNAJC9, a J-domain protein as a lead candidate from the screen and showed that cells depleted for DNAJC9 exhibit mislocalization of CENP-A, enrichment of CENP-A in chromatin, and CIN phenotypes. Global interactome analysis showed an enhanced interaction of CENP-A with the replication-associated H3-H4 chaperone MCM2 in DNAJC9-depleted cells and co-depletion of MCM2 and DNAJC9 suppressed CENP-A mislocalization. Furthermore, we showed that cells ablated for the ability of DNAJC9 to promote the proper folding of H3–H4, exhibit CENP-A mislocalization. CUT&RUN Sequencing analysis of genome-wide CENP-A occupancy in DNAJC9-depleted cells identified 16,603 sites of non-centromeric localization, that broadly overlapped with open chromatin regions. Our comprehensive analysis has identified factors that prevent mislocalization of CENP-A and has defined DNAJC9 as an important safeguard that prevents CENP-A mislocalization and CIN.
2024-03-26 | GSE253387 | GEO
Project description:Silencing of Germline-Expressed Genes by DNA Elimination in Somatic Cells
| PRJNA168099 | ENA
Project description:Mislocalization of CENP-A to non-centromeric regions contributes to chromosomal instability (CIN). Here, we defined a role for the histone H3/H4 chaperone CHAF1B in preventing mislocalization of CENP-A and CIN.
2023-05-05 | GSE227373 | GEO
Project description:Eukaryotic cells express several classes of small RNAs that regulate gene expression and ensure genome maintenance. Endogenous siRNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs) mainly control gene and transposon expression in the germline, while microRNAs (miRNAs) generally function in post-transcriptional gene silencing in both somatic and germline cells. To provide an evolutionary and developmental perspective on small RNA pathways in nematodes, we identified and characterized known and novel small RNA classes through gametogenesis and embryo development in the parasitic nematode Ascaris suum and compared them with known small RNAs of Caenorhabditis elegans. piRNAs, Piwi-clade Argonautes, and other proteins associated with the piRNA pathway have been lost in Ascaris. miRNAs are synthesized immediately following fertilization in utero, prior to pronuclear fusion, and before the first cleavage of the zygote. This is the earliest expression of small RNAs ever described at a developmental stage long thought to be transcriptionally quiescent. A comparison of the two classes of Ascaris endo-siRNAs, 22G-RNAs and 26G-RNAs, to those in C. elegans, suggests great diversification and plasticity in the use of small RNA pathways during spermatogenesis in different nematodes. Our data reveal conserved characteristics of nematode small RNAs as well as features unique to Ascaris that illustrate significant flexibility in the use of small RNAs pathways, some of which are likely an adaptation to Ascaris’ life cycle and parasitism.
2011-06-16 | GSE26956 | GEO