Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AR cooperates with SMAD4 to maintain muscle homeostasis

ABSTRACT: The goal of this study was to determine the mechanism of androgne in driving muscle hypertrophy programmes. CONCLUSION: AR transcriptionally cooperates with SMAD4 and this affect is lost in the presence of expansion of the polyglutamine repeat in the AR gene.

ORGANISM(S): Mus musculus

PROVIDER: GSE185977 | GEO | 2022/05/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

AR cooperates with SMAD4 to maintain muscle homeostasis

Project description:AR cooperates with SMAD4 to maintain muscle homeostasis

| PRJNA771642 | ENA

AR cooperates with SMAD4 to maintain skeletal muscle homeostasis.

Project description:Androgens and androgen-related molecules exert a plethora of functions across different tissues, mainly through binding to the transcription factor androgen receptor (AR). Despite widespread therapeutic use and misuse of androgens as potent anabolic agents, the molecular mechanisms of this effect on skeletal muscle are currently unknown. Muscle mass in adulthood is mainly regulated by the bone morphogenetic protein (BMP) axis of the transforming growth factor (TGF)-β pathway via recruitment of mothers against decapentaplegic homolog 4 (SMAD4) protein. Here we show that, upon activation, AR forms a transcriptional complex with SMAD4 to orchestrate a muscle hypertrophy programme by modulating SMAD4 chromatin binding dynamics and enhancing its transactivation activity. We challenged this mechanism of action using spinal and bulbar muscular atrophy (SBMA) as a model of study. This adult-onset neuromuscular disease is caused by a polyglutamine expansion (polyQ) in AR and is characterized by progressive muscle weakness and atrophy secondary to a combination of lower motor neuron degeneration and primary muscle atrophy. Here we found that the presence of an elongated polyQ tract impairs AR cooperativity with SMAD4, leading to an inability to mount an effective anti-atrophy gene expression programme in skeletal muscle in response to denervation. Furthermore, adeno-associated virus, serotype 9 (AAV9)-mediated muscle-restricted delivery of BMP7 is able to rescue the muscle atrophy in SBMA mice, supporting the development of treatments able to fine-tune AR-SMAD4 transcriptional cooperativity as a promising target for SBMA and other conditions associated with muscle loss.

| S-EPMC9107400 | biostudies-literature

Smad4 deficiency impairs chondrocyte hypertrophy via the Runx2 transcription factor in mouse skeletal development [ChIP-seq]

Project description:Smad4 is a central mediator of canonical TGF/BMP signaling and plays important roles in mesenchymal cell aggregation, chondrocyte differentiation, osteoblast differentiation and maturation. However, the regulatory mechanism of Smad4 underlying chondrocyte hypertrophy during skeletal development is unknown. To elucidate the molecular mechanism by which Smad4 deficiency impairs chondrocyte hypertrophy, we performed high-throughput Chip-seq to identify target genes involved in Smad4-regulated chondrocyte hypertrophy. Our results suggest that Smad4 controls chondrocyte hypertrophy through regulating Runx2 expression during skeletal development.

2018-05-07 | GSE114081 | GEO

Smad4 deficiency impairs chondrocyte hypertrophy via the Runx2 transcription factor in mouse skeletal development [RNA-seq]

Project description:Smad4 is a central mediator of canonical TGF/BMP signaling and plays important roles in mesenchymal cell aggregation, chondrocyte differentiation, osteoblast differentiation and maturation. However, the regulatory mechanism of Smad4 underlying chondrocyte hypertrophy during skeletal development is unknown. To elucidate the molecular mechanism by which Smad4 deficiency impairs chondrocyte hypertrophy, we performed high-throughput RNA-seq to identify target genes involved in Smad4-regulated chondrocyte hypertrophy. Our results suggest that Smad4 controls chondrocyte hypertrophy through regulating Runx2 expression during skeletal development.

2018-05-07 | GSE114079 | GEO

AR function is altered by polyglutamine expansion and by SUMO

2014-08-23 | GSE50383 | GEO

AR function is altered by polyglutamine expansion and by SUMO

Project description:Expansion of a polyglutamine (polyQ) tract in the gene for the androgen receptor (AR) results in partial loss of transactivation function and causes spinobulbar muscular atrophy (SBMA). Modification of AR by small ubiquitin-like modifier (SUMO) reduces AR function in a promoter context-dependent manner. We used microarrays to confirm and demonstrate loss of AR function from polyQ expansion and to test the degree to which AR function is altered by preventing polyQ AR SUMOylation. PC12 cells expressing AR10Q, AR112Q, or nonSUMOylatable AR112Q (KRKR) in the presence or absence of synthetic androgen R1881 were assessed for alterations in AR function by comparing gene expression changes with each AR variant in response to ligand.

2014-08-23 | E-GEOD-50383 | biostudies-arrayexpress

RNA-Seq results of a neuronal cell model of SBMA, AR-97Q cells, compared to AR-24Q cells

Project description:Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by a polyglutamine expansion in the androgen receptor (AR). Transcriptional changes were compared between a muscle cell model of SBMA (AR-97Q cells) and a control model (AR-24Q cells). RNA-seq gene expression analysis revealed that differentially expressed genes were associated with upregulation of transforming growth factor β (TGFβ) signaling, mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF) signaling, calcium signaling, and NFκB signaling.

2024-11-05 | GSE252533 | GEO

SMAD4 lossdifferentlyshapespancreatictumorswithdistinct KRASmutations

Project description:We compared KPC Smad4 WT and Smad4 KO tumours from orthotopically-grafted organoid-derived mouse models

2024-12-02 | GSE274684 | GEO

SMAD4 lossdifferentlyshapespancreatictumorswithdistinct KRASmutations

Project description:SMAD4 lossdifferentlyshapespancreatictumorswithdistinct KRASmutations

| PRJNA1147660 | ENA

ChIP-seq study using a cell line model of ER_ AR+ molecular apocrine tumours (AR_FoxA1_molecular_apocrine)

Project description:Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER_ AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER_ AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.

2012-02-18 | E-MTAB-986 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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