Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise.

ABSTRACT: Inbred individuals reared in controlled environments display considerable variance in many complex traits. The underlying cause of this variability has been an enigma, hence the term intangible variation. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process. Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28), show greater coefficients of variance in body weight than their wildtype littermates. Inbred mice carrying a mutation in Trim28 develop metabolic syndrome and abnormal behaviour with incomplete penetrance. These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans.

ORGANISM(S): Mus musculus

PROVIDER: GSE23512 | GEO | 2010/11/15

SECONDARY ACCESSION(S): PRJNA131085

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise.

Project description:Inbred individuals reared in controlled environments display considerable variance in many complex traits. The underlying cause of this variability has been an enigma, hence the term intangible variation. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process. Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28), show greater coefficients of variance in body weight than their wildtype littermates. Inbred mice carrying a mutation in Trim28 develop metabolic syndrome and abnormal behaviour with incomplete penetrance. These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans. Liver gene expression in Trim28MommeD9 heterozygotes compared to wildtype littermates.

2010-11-15 | E-GEOD-23512 | biostudies-arrayexpress

TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression [microarray]

Project description:In this study, proteomic profiling of TRIM24 interactome in conjunction with shRNA screening of TRIM24 top-interactors nominated that TRIM28 is indispensable for TRIM24 protein stability. We showed that TRIM28 stabilizes TRIM24 against SPOP-mediated ubiquitination and degradation. TRIM28 promotes TRIM24 and AR transcription activity, androgen-dependent and -independent PCa growth. In addition, we demonstrated that TRIM28 level in high in advanced PCa, which drives TRIM24/AR transcription activity in a similar manner to SPOP mutation, which implies that TRIM28 potentially dictates the therapeutic outcome of TRIM24-targeted therapy.

2018-10-05 | GSE108145 | GEO

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise.

Project description:Inbred individuals reared in controlled environments display considerable variance in many complex traits but the underlying cause of this intangible variation has been an enigma. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process.Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28) show greater coefficients of variance in body weight than their wild-type littermates. Trim28 mutants additionally develop metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide gene expression analyses identified 284 significantly dysregulated genes in Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes a G-protein coupled receptor implicated in lipid metabolism, showing the greatest average change in expression (7.8-fold higher in mutants). This gene also showed highly variable expression between mutant individuals.These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans.

| S-EPMC3156950 | biostudies-literature

TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression [ChIP-seq]

2018-10-05 | GSE108144 | GEO

TRIM28 is essential for erythroblast differentiation in the mouse

Project description:We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia.We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28 we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow. To induce Cre recombinase from the Mx1Cre transgene, poly(I:C) was injected 5 times every other day. Mice were analyzed two weeks after completion of poly(I:C) administration. TRIM28 mutant mice generate two distinct types of immature erythroid cells; KOa, with 5-8% of the Trim28 gene remaining undeleted (still bearing 26% of residual mRNA), and KOb, with 1-4% of the gene remaining undeleted (and with 18% of mRNA remaining).

2013-10-04 | E-GEOD-49843 | biostudies-arrayexpress

RNA-seq of gonadal adipose tissue from male and female Trim28-WT and Trim28 adipose specific KO mice

Project description:Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. We set out to determine if adipose specific deletion of Trim28 led to changes in adipose tissue function and molecular phenotype. We performed transcriptomics analysis on adipose tissue taken from WT and adipose specific Trim28 KO mice to investigate their molecular phenotype, and to identify pathways altered in KO animals.

2020-11-25 | E-MTAB-9809 | biostudies-arrayexpress

TRIM28 silences endogenous retroviruses in neural progenitor cells

Project description:Here we show that in neural progenitor cells (NPCs) TRIM28 silences transcription of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. Derepression of ERVs in Trim28-deficient NPCs was associated with a loss of H3K9me3 and resulted in transcriptional upregulation and reverse transcription. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Analysis of upregulation of ERVs in Trim28-deficient NPCs

2015-01-07 | E-GEOD-45930 | biostudies-arrayexpress

TRIM28 regulates RNA polymerase II promoter proximal pausing and entry into processive elongation

Project description:Analysis of total PolII and Ser2-phosphorylated PolII genomic occupancy in control-transfected (WT) or Trim28-knockdown (Trim28-KD) embryonic stem cells. Embryonic stem cells were transfected with luciferase siRNA (WT) or Trim28 siRNA (Trim28 KD) in duplicate experiments. 48 hrs after transfection, cells were crosslinked with formaldehyde, collected, lysed, and chromatin was fragmented with sonication. Total PolII or Ser2-phosphorylated PolII genomic occupancy in WT or Trim28 KD cells were determined by ChIP-seq.

2014-07-28 | E-GEOD-48253 | biostudies-arrayexpress

WTX interacts with the transcriptional regulator TRIM28 to mediate cellular differentiation

Project description:WTX encodes a tumor suppressor implicated in Wilms tumor and in mesenchymal differentiation, with distinct functions in the cytoplasm, at the plasma membrane and in the nucleus. Here we report that the transcriptional corepressor TRIM28 is the major binding partner for nuclear WTX. The WTX-TRIM28 interaction supports chromatin binding by TRIM28, enhancing transcriptional silencing of some TRIM28 target sequences. In mouse ES cells, where TRIM28-mediated silencing of repetitive sequences is best characterized, Wtx knockdown similarly derepresses endogenous retroviruses and LINE elements. We performed digital gene expression (DGE) profiling using Helicos RNA sequencing. Helicos sequencing does not involve an amplification step, hence it has less bias, especially in sequencing of repetitive elements. We sequenced RNA extracted from mouse ESCs harboring GFP, Wtx or Trim28 hairpins. The resulting sequence reads were aligned with the RefSeq database as well as Repbase, which is a database for the repetitive sequences.

2015-04-16 | E-GEOD-60418 | biostudies-arrayexpress

TRIM28 modulates nuclear receptor signaling to regulate uterine function

Project description:This project identified that TRIM28 can modulate progesterone and estrogen signaling in both human and mouse endometrium to regulate its normal functions during pregnancy. TRIM28 showed proximal localization and co-immunoprecipitation with PR and ERalpha. The ablation of TRIM28 can inhibit the chromatin binding activity of PR and ERalpha leading to disrupted estrogen and progesterone signaling. This immunoprecipitation using TRIM28 antibody was performed in pre-decidual human endometrial stromal cells (HESCs) without any hormone treatment. The potential interacting proteins of TRIM28 was analyzed using mass spec.

2023-07-05 | MSV000092346 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data