Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transgenerational self-reconstruction of disrupted chromatin organization after exposure to an environmental stressor in mice

ABSTRACT: Exposure to environmental stressors is known to increase disease susceptibility in unexposed descendants in the absence of detectable genetic mutations. The mechanisms mediating environmentally-induced transgenerational disease susceptibility are poorly understood. We showed that great-great-grandsons of female mice exposed to tributyltin (TBT) throughout pregnancy and lactation were predisposed to obesity due to altered chromatin organization that subsequently biased DNA methylation and gene expression. Here we analyzed DNA methylomes and transcriptomes from tissues of animals ancestrally exposed to TBT spanning generations, sexes, ontogeny, and cell differentiation state. We found that TBT elicited concerted alterations in the expression of “chromatin organization” genes and inferred that TBT-disrupted chromatin organization might be able to self-reconstruct transgenerationally. We also found that the location of “chromatin organization” and “metabolic” genes is biased similarly in mouse and human genomes, suggesting that exposure to environmental stressors in different species could elicit similar phenotypic effects via self-reconstruction of disrupted chromatin organization.

ORGANISM(S): Mus musculus

PROVIDER: GSE136377 | GEO | 2019/08/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transgenerational self-reconstruction of disrupted chromatin organization after exposure to an environmental stressor in mice

Project description:Transgenerational self-reconstruction of disrupted chromatin organization after exposure to an environmental stressor in mice

| PRJNA562316 | ENA

Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice

Project description:Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants, adding a layer of complexity to long-standing attempts to clarify the relationships between genotypic and phenotypic variations. Transgenerational inheritance of environmental exposures has significant implications for understanding disease etiology. The environmental obesogen hypothesis proposes that exposure to obesogenic chemicals can lead to increased adiposity, in vivo. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the TBT-dependent F4 obesity is consistent with a leptin resistant, "thrifty phenotype". We found that ancestral TBT exposure induced global changes in DNA methylation together with altered expression of metabolism-relevant genes when the animals were exposed to dietary challenges. Analysis of chromatin accessibility in sperm revealed significant differences between DMSO and TBT groups when guided by DNA sequence composition, a proxy for higher order chromatin organization. Taken together, these data establish an independent connection between ancestral TBT treatment and altered chromatin accessibility that may reflect changes in higher order chromatin organization transmissible through meiosis and mitosis.

2017-11-10 | GSE105051 | GEO

Phaeo CDF 2011 - stressor exposed vs control

Project description:Initial work for profiling contaminant response in Phaeodactylum cells exposed to contaminants and non contaminant stressors

2012-01-11 | GSE34988 | GEO

Phaeo CDF 2011 - stressor exposed vs control

Project description:Initial work for profiling contaminant response in Phaeodactylum cells exposed to contaminants and non contaminant stressors Two colour arrays: Control versus exposed. 5 biological replicates per treatment, 6 split controls one replicate per array

2012-01-11 | E-GEOD-34988 | biostudies-arrayexpress

Epigenome-Wide Association Study for Transgenerational Disease Epimutation Sperm Biomarkers following Ancestral Exposure to Jet Fuel Hydrocarbons

Project description:Jet fuel hydrocarbons is the generic name for aviation fuels used in gas-turbine engine powered aircrafts. Due to the widespread use of jet fuel hydrocarbons, this compound has been recognized as the single largest chemical exposure for military personnel. Previous animal studies have demonstrated the ability of jet fuel (JP-8) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The diseases observed include late puberty, kidney, obesity and multiple disease pathologies. The current study was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations identify few disease specific differential DNA methylation regions (DMRs) called epimutations in the transgenerational F3 generation great-grand-offspring rats ancestrally exposed to jet fuel. The potential epigenetic DMRs were identified for late puberty, kidney, obesity, and multiple diseases, and found to be predominantly disease specific. These disease specific DMRs have associated genes previously shown to be linked with each of these specific diseases. Therefore, the germline (i.e. sperm) has environmentally induced ancestrally derived epimutations that have the potential to transgenerationally transmit disease susceptibilities to subsequent generations. Epigenetic biomarkers for specific diseases could be developed as medical diagnostics to facilitate clinical management of disease and allow preventative medicine therapeutics.

2020-10-01 | GSE155922 | GEO

Germ cell epigenetic instability in the Mtrr mouse model of transgenerational epigenetic inheritance

Project description:Folate metabolism is important for the generation of methyl groups required for cellular methylation reactions. Mice with a hypomorphic mutation in the gene Mtrr have disrupted folate metabolism and show transgenerational inheritance of developmental abnormalities. We sought to explore if DNA methylation patterns in the sperm of Mtrr mice may be disrupted. Therefore we performed MeDIP-seq on sperm collect from males with the Mtrr mutation (either heterozygous (Mtrr +/gt) or homozygous mutants (Mtrr gt/gt)), males ancestrally exposed to the Mtrr mutation (Mtrr +/+) and C57Bl/6J control males. C57Bl/6J males were used as controls as they have the same genetic background as the mice with Mtrr mutation.

2021-04-06 | E-MTAB-8533 | biostudies-arrayexpress

miR-223 Plays A Critical Role in Obesogen-Enhanced Adipogenesis in Mesenchymal Stem Cells and Transgenerational Obesity

Project description:Exposure of pregnant F0 mouse dams to the obesogen tributyltin (TBT) predisposes unexposed male descendants to obesity and diverts mesenchymal stem cells (MSCs) toward the adipocytic lineage. TBT also promotes adipogenic commitment and differentiation of MSCs, in vitro. We sought to identify TBT-induced factors predisposing MSCs toward the adipocytic fate. We exposed mouse MSCs to TBT, the PPARγ-selective agonist rosiglitazone or the RXR-selective agonist LG-100268 and determined their transcriptomal profiles to determine candidate microRNAs (miR) regulating adipogenic commitment and differentiation. Of the top 10 candidate microRNAs predicted by Ingenuity Pathway Analysis, miR-21, miR-33 and miR-223 were expressed to regulate genes differentially expressed in adipogenesis. After exposing to 50 nM TBT for 24 hours, miR-223 levels of MSCs were increased and expression of its target genes ZEB1, NFIB, and FOXP1 decreased. Both ROSI and TBT increased miR-223 levels, and this induction was inhibited by PPARγ antagonists (T0070907) but not RXR antagonists (HX531, UVI3003), placing miR-223 downstream of PPARγ. Chromatin immunoprecipitation confirmed TBT-induced binding of PPARγ to regulatory elements in the miR-223 promoter. miR-223 levels were elevated in ancestral TBT exposed F2 and F3 male adipose tissues and further increased when animals were fed with a high fat diet. TBT induced miR-223 expression and adipogenesis in MSCs through the PPARγ pathway and promoted elevated miR-223 expression in white adipose tissue of F2 and F3 male descendants of F0 treated dams. This shows that transgenerationally increased expression of miR-223 plays an important role in the transmission of the obese phenotype after TBT exposure.

2022-10-27 | GSE216429 | GEO

Transgenerational transcriptomic and DNA methylome profiling of mouse fetal testicular germline and somatic cells after exposure of pregnant mothers to tributyltin, a potent obesogen

Project description:Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) that were never exposed. To address the effects of TBT exposure on germ cells, we exposed pregnant transgenic OG2 mouse dams (F0), which specifically express EGFP in germline cells, to an environmentally relevant dose of TBT throughout gestation through drinking water. When fed with a high fat diet (HFD), F3 male offspring of TBT-exposed F0 dams (TBT-F3) accumulated much more body fat than did Control-F3 males. TBT-F3 males also lost more body fluid and lean compositions than did Control-F3 males. Expression of genes involved in transcriptional regulation or mesenchymal differ-entiation was upregulated in somatic cells of TBT-F1 (but not TBT-F3) E18.5 fetal testes, and promoter-associated CpG islands were hyper-methylated in TBT-F1 somatic cells. Global mRNA expression of protein-coding genes in F1 or F3 fetal testicular cells was unaffected by F0 exposure to TBT; however, expression of a subset of endogenous retroviruses was significantly affected in F1 and F3. We infer that TBT may directly target testicular somatic cells in F1 testes to irreversibly affect epigenetic suppression of endogenous retroviruses in both germline and somatic cells.

2022-03-02 | GSE191199 | GEO

Molecular genomic studies of the obesogenic effects of tributyltin during adipogenic differentiation implicate a primary role for cytoskeletal damage [RNA-seq]

Project description:Environmental obesogens are being studied for their potential role in the increasing prevalence of obesity globally. A major area of focus in this field of research has been on the mechanism by which these agents act. In this study we focused on the organotin tributyltin (TBT), a water pollutant exposed to humans through diet. The mechanism by which TBT is believed to act is by binding to the PPAR nuclear receptor which heterodimerizes with RXR to alter gene regulation. To test whether this was the dominant mechanism for TBT activity, we performed time-course studies of transcription and chromatin accessibility in mesenchymal stem cells differentiating to adipocytes. We found limited evidence for PPAR effects by TBT, but a strong response by Ras-related GTPases and evidence for the loss of TEAD transcription factor activity during differentiation. These observations combine to implicate a known property of organotins, to cause cytoskeletal depolymerization. We propose a model for TBT activity involving a primary effect of cytoskeletal damage, leading to the loss of YAP co-regulator activity and the consequent failure of TEAD repression of adipogenesis.

2024-01-01 | GSE207038 | GEO

Molecular genomic studies of the obesogenic effects of tributyltin during adipogenic differentiation implicate a primary role for cytoskeletal damage [ATAC-seq]

2024-01-01 | GSE207039 | GEO