Loss of ARNT Impair Adaptability of Muscular Exercise in Aged Mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA656121 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12417610_1.fastq.gz | Fastqsanger.gz | |||
| SRR12417610_2.fastq.gz | Fastqsanger.gz | |||
| SRR12417611_1.fastq.gz | Fastqsanger.gz | |||
| SRR12417611_2.fastq.gz | Fastqsanger.gz | |||
| SRR12417612_1.fastq.gz | Fastqsanger.gz |
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Project description:The adaptation of regimented exercise in skeletal muscle including muscular hypertrophy and enhanced strength decline significantly with aging. Transcriptome analysis following RNA sequencing reveals extensive activation of hypoxia-related genes in young exercised mice versus the sedentary, but absent in aged exercised mice. Particularly, less expression of aryl hydrocarbon receptor translocator (ARNT) was observed in response to exercise in aged mice. Young mice underwent skeletal muscle-specific knockout of ARNT (ARNT mKO) obtain deficient benefit from exercise resembling the aged mice. The deletion of ARNT associated with decreased expression of Notch1 intracellular domain(N1ICD) impair muscle hypertrophy and regeneration. Administration of ML228, a systematic agonist of ARNT, rescued skeletal muscle adaptabilities in old mice, which was suppressed by administrating N1ICD inhibitor(DAPT). These results suggest that the loss of skeletal muscle ARNT is partially responsible for diminished response to exercise in aging and activation of hypoxia signaling holds promise for rescuing the adaptability in aged muscle.
2021-12-31 | GSE155937 | GEO
Project description:The aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) activated complex regulates genes in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR has also emerged as a potential therapeutic target for the treatment of human diseases and different cancers, including breast cancer. To better understand AHR and ARNT signaling in breast cancer cells, we used chromatin immunoprecipitation linked to high throughput sequencing to identify AHR- and ARNT-binding sites across the genome in TCDD treated MCF-7 cells. We identified 2,594 AHR-bound, 1,352 ARNT-bound and 882 high confidence AHR/ARNT co-bound regions. No significant differences in the genomic distribution of AHR and ARNT were observed. Approximately 60% of the co-bound regions contained at least one core AHRE, 5'-GCGTG-3'. AHR/ARNT peak density was the highest within 1 kb of transcription start sites (TSS); however, a number of AHR/ARNT co-bound regions were located as far as 100 kb from TSS. De novo motif discovery identified a symmetrical variation of the AHRE (5'-GTGCGTG-3'), as well as FOXA1 and SP1 binding motifs. Microarray analysis identified 104 TCDD responsive genes where 98 genes were up-regulated by TCDD. Of the 104 regulated genes, 69 (66.3%) were associated with an AHR- or ARNT-bound region within 100 kb of their TSS. Overall our study identified AHR/ARNT co-bound regions across the genome, revealed the importance but not absolute requirement for an AHRE in AHR/ARNT interactions with DNA, and identified a modified AHRE motif, thereby increasing our understanding of AHR/ARNT signaling pathway. Examination of genome-wide AHR and ARNT binding pattern in MCF-7
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Project description:To study the combined effect of myostatin/activin inhibition and exercise on muscle mass and pathophysiology, young mdx mice, a model for Duchenne Muscular Dystrophy, were injected with soluble activin receptor-Fc (sActRIIB-Fc) or placebo (PBS) 1x/week for a 7-week period, in combination with or without voluntary running. C57Bl/10ScSnJ mice injected with PBS acted as wildtype controls. Microarray expression analysis from skeletal muscle was performed using m. gastrocnemies as the sample. We found thatexercise or a combination of exercise and sActRIIB-Fc treatment is more effective in correcting gene expression profiles of dystrophic muscles than the sActRIIB-Fc treatment alone. We also identified several pathways and proteins that were affected by exercise and sActRIIB-Fc together or independently. Total RNA obtained from gastrocnemius muscle of mdx mice divided into four groups: 1) control (injected with PBS, n=5), 2) runners (voluntary wheel running for 7 weeks, injected with PBS, n=5), 3) sActRIIB-Fc -treated (n=5), and 4) runners with sActRIIB-Fc-treatment (n=5). sActRIIB-Fc or PBS was injected intraperitoneally once a week with a 5-mg/kg dose of sActRIIB-Fc. In addition, wildtype mice served as healthy controls (n=4).
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Project description:The aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) activated complex regulates genes in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR has also emerged as a potential therapeutic target for the treatment of human diseases and different cancers, including breast cancer. To better understand AHR and ARNT signaling in breast cancer cells, we used chromatin immunoprecipitation linked to high throughput sequencing to identify AHR- and ARNT-binding sites across the genome in TCDD treated MCF-7 cells. We identified 2,594 AHR-bound, 1,352 ARNT-bound and 882 high confidence AHR/ARNT co-bound regions. No significant differences in the genomic distribution of AHR and ARNT were observed. Approximately 60% of the co-bound regions contained at least one core AHRE, 5'-GCGTG-3'. AHR/ARNT peak density was the highest within 1 kb of transcription start sites (TSS); however, a number of AHR/ARNT co-bound regions were located as far as 100 kb from TSS. De novo motif discovery identified a symmetrical variation of the AHRE (5'-GTGCGTG-3'), as well as FOXA1 and SP1 binding motifs. Microarray analysis identified 104 TCDD responsive genes where 98 genes were up-regulated by TCDD. Of the 104 regulated genes, 69 (66.3%) were associated with an AHR- or ARNT-bound region within 100 kb of their TSS. Overall our study identified AHR/ARNT co-bound regions across the genome, revealed the importance but not absolute requirement for an AHRE in AHR/ARNT interactions with DNA, and identified a modified AHRE motif, thereby increasing our understanding of AHR/ARNT signaling pathway.
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Project description:The aryl hydrocarbon receptor (AHR) is an important hepatic transcription factor that appears to have a role in regulating endogenous liver metabolism. Canonical AHR-mediated regulation of transcription requires AHR binding to its DNA-binding partner, the AHR nuclear translocator (ARNT). We previously demonstrated that the AHR can regulate transcription independent of ARNT via “non-canonical” interactions with Kruppel-like factor 6, and that hepatic AHR loss can protect against high-fat diet (HFD) challenge. In this study, we examined the effects of hepatic AHR or ARNT loss in HFD-fed mice to determine whether AHR regulation of liver metabolism might partially occur independent of ARNT. The data show that similar to AHR loss, ARNT loss reduces HFD-driven hepatic lipid deposition, but does not recapitulate the diminished weight gain and adiposity observed in AHR KO animals. Utilizing transcriptomic sequencing analyses, we uncovered specific gene pathways that likely account for these phenotypic differences/similarities associated with AHR or ARNT loss. Together, these data highlight the physiological significance of ARNT-independent AHR activity, and identify discrete aspects of liver metabolism likely regulated via canonical AHR action.
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