The X-chromosome dosage compensation program during the development of cynomolgus monkeys
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PROVIDER: PRJNA634892 | ENA |
REPOSITORIES: ENA
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Project description:X-chromosome dosage compensation ensures balanced gene dosage between the X chromosome and autosomes and between the sexes, involving divergent mechanisms among mammals. We elucidated a distinct mechanism for X-chromosome inactivation (XCI) in cynomolgus monkeys, a model for human development. The trophectoderm and cytotrophoblast acquire XCI around implantation through an active intermediate bearing repressive modifications and compacted structure, whereas the amnion, epiblast, and hypoblast maintain such an intermediate protractedly, attaining XCI by a week after implantation. Males achieve X-chromosome up-regulation (XCU) progressively, whereas females show XCU coincidentally with XCI, both establishing the X:autosome dosage compensation by 1 week after implantation. Conversely, primordial germ cells undergo X-chromosome reactivation by reversing the XCI pathway early during their development. Our findings establish a foundation for clarifying the dosage compensation mechanisms in primates, including humans.
2021-11-19 | GSE151149 | GEO
Project description:Studying X-chromosome dosage compensation dynamics in human early embryos using single cell RNA sequencing
2019-10-24 | GSE130050 | GEO
Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls.
2023-06-23 | PXD036423 | Pride
Project description:EXPERIMENT: The animal experiments were performed at Shin Nippon Biomedical Laboratories (SNBL), Ltd. (Kagoshima, Japan) in compliance with the Guideline for Animal Experimentation (1987), and in accordance with the Law Concerning the Protection and Control of Animals (1973) and the Standards Relating to the Care and Management of Experimental Animals (1980). This study was approved by the Institutional Animal Care and Use Committee of SNBL and performed in accordance with the ethics criteria contained in the bylaws of the SNBL committee. Each female monkey was paired with a male of proven fertility for one day between day 11 and day 15 of the menstrual cycle. Pregnant females, aged 5-8 years and weighing 2.84-3.76 kg on day 22 of gestation, were allocated randomly to two groups, each with three monkeys, and housed individually. The monkeys were orally dosed with (±)-thalidomide (Lot no. SDH7273/SDJ3347, Wako Pure Chemical Industries, Ltd., Osaka, Japan) at 0 or 20 mg/kg by oral intubation on day 26 of gestation, which was during the critical period for thalidomide-induced teratogenesis [Delahunt and Lassen, 1964; Hendrickx, 1973]. Dosage was adjusted to the body weight on day 22 of gestation and the drug was packed in a gelatin capsule. Control monkeys received the capsule only. ANIMAL MODEL: Macaca fascicularis INTERVAL: NON. PLATFORM: Proprietary Affymetrix NHP GeneChip® Array for Cynomolgus genome derived from Biogen Idec Keywords = Developmental Keywords = Monkeys Keywords = Thalidomide TFetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomidechannel oligonucleotide (Affymetrix) platform.
2010-06-20 | E-GEOD-15542 | biostudies-arrayexpress
Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. To evaluate organ transcriptomes and gene expression variability in Cynomolgus monkeys, we used Customized NimbleGen Microarrays (Design ID: 120419_Cynomolgus_v5_TH_exp_HX12) for genome-wide gene expression profiling on 5 different tissues (heart, kidney, liver, lung, spleen) from 21 Cynomolgus monkeys. Cynomolgus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 females and 2 males), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore, genome-wide copy number variation was analyzed in tissue samples from the same animals using a custom NimbleGen 4.2 million probes comparative genomic hybridization (CGH) array to associate CNV genotypes with expression changes of proximal genes.
2016-02-24 | GSE76560 | GEO
Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. Cynomolgus monkeys are outbred species and exhibit substantial levels of genetic variation which can affect the outcome and interpretation of biomedical studies. Copy number variations (CNVs) are a significant source of genetic diversity and a comprehensive understanding of the genomic impact of CNVs on phenotypic traits is limited. A custom 4.2 million probes comparative genomic hybridization (CGH) array (Design-ID: 120405_Cynomolgus5_CGH_UX1) has been designed on the basis of the Cynomolgus monkey genome (Ebeling et al. (2011) Genome Research; PMID: 21862625) to assess genome-wide copy number variation among Cynomolgus monkeys. Using Cynomolgus monkey specific NimbleGen CGH Microarrays we profiled the genomes of 21 Cynomolgus monkeys. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. Cynomolus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 males and 2 females), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore genome-wide expression profiles were analyzed in 5 vitally important tissue samples (heart, kidney, liver, lung, spleen) from the same animals using a custom Cynomolgus monkey specific NimbleGen gene expression microarray (design ID: 120419_Cynomolgus_v5_TH_exp_HX12) to associate CNV genotypes with expression changes of proximal genes using a cis expression quantitative trait loci (cis-eQTL) mapping approach. Expression data have been deposited at the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE76560. The array CGH results analyzed in this study are further described in Gschwind A.R. et al. (2016) "Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis". under submission
2016-02-24 | GSE76707 | GEO
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128566 | GEO
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128564 | GEO
Project description:Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X-chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-size topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundary locations. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating one rex site is necessary and sufficient for DCC-dependent boundary formation. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor consequence of gene repression during dosage compensation. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in regulating stress responses and aging.
2019-09-05 | GSE128559 | GEO
Project description:We have conducted a global analysis of somatic dosage compensation and also asked if germ cell dosage compensate by microarray analysis of gene expression in wild-type tissues. To obviate the confounding effects of scatter and especially the skewed genomic distributions of genes with sex-biased expression in both the soma and germline [there are fewer X chromosome genes with male-biased expression], we used mutations that transform sexual identity. In the soma we used gain-of-function transformer to turn X;AA flies into somatic females with tumorous germlines. The gonadectomized somas of these X;AA female flies were compared to similarly prepared XX;AA females. The X;AA ovarian tumors, which are possibly the result of germline sex transformations, were compared to the similar XX;AA ovarian tumors generated with loss-of-function alleles of ovarian tumor and Sex-lethal. We used alleles of transformer-2 and doublesex to transform XX;AA flies into somatic males with atrophic germlines. Keywords: other
2005-12-15 | GSE2119 | GEO