Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Experimental Design
2.3. Immunochemistry
2.4. Morphometric and Statistical Analysis
2.5. RNA Isolation
2.6. CAGE-Seq
2.7. Data Analysis
2.7.1. Quality Control
2.7.2. Genome, Annotation, and Indexing
2.7.3. Read Mapping
2.7.4. CTSS Aggregation
2.7.5. TSS Peaks
2.7.6. Enhancers
2.7.7. Annotation of TSS Peaks to Genes and Enhancers
2.7.8. Differentially Expressed Peaks, Genes, and Enhancers
2.7.9. Gene Set Enrichment Analysis (GSEA)
3. Results and Discussion
3.1. Morphometric Analysis Confirms Distinct Disuse Associated Remodeling in Slow, but Not Fast Muscles
3.2. Integrative Database of Rat’s Regulatory Elements with a Focus on Muscles
3.3. Muscle Atrophy and Recovery are Associated with Large Changes in the Unique Gene Set Expression Profiles, with Distinct Dynamics on Each Stage
3.4. Gene Enrichment Analysis Reveals that Adaption to Disuse Processes in Slow and Fast Muscles is Mediated by Different Molecular Pathways
3.5. Tissue-Specific Intergenic TSS Show Different Patterns in Slow and Fast Muscles and Widely Co-Express with Coding Genes in Response to Disuse
3.6. Alternative Usage of Dominating Transcription Starting Sites in Differentially Expressed Genes
3.7. Expression of Transcribed Enhancers in Rat Skeletal Muscles is Linked to Disuse-Recovery Cycle
3.7.1. Differentially Expressed Enhancers Mediate Muscle-Specific Transcription Program
3.7.2. Switch ON/OFF Enhancers on First Day of Recovery (R1)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CAGE | Cap Analysis Gene Expression |
CSA | Cross-Sectional Area |
CTSS | CAGE Tag Start Sites |
DPI1 | Decomposition-Based Peak Identification |
EDL | Extensor Digitorum Longum |
eRNA | enhancer RNA |
GSEA | Gene Set Enrichment Analysis |
LFC | Log2 Fold Change |
RFU | Relative Fluorescent Units |
TSS | Transcription Start Sites |
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Pintus, S.S.; Akberdin, I.R.; Yevshin, I.; Makhnovskii, P.; Tyapkina, O.; Nigmetzyanov, I.; Nurullin, L.; Devyatiyarov, R.; Shagimardanova, E.; Popov, D.; et al. Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle. Biology 2021, 10, 557. https://doi.org/10.3390/biology10060557
Pintus SS, Akberdin IR, Yevshin I, Makhnovskii P, Tyapkina O, Nigmetzyanov I, Nurullin L, Devyatiyarov R, Shagimardanova E, Popov D, et al. Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle. Biology. 2021; 10(6):557. https://doi.org/10.3390/biology10060557
Chicago/Turabian StylePintus, Sergey S., Ilya R. Akberdin, Ivan Yevshin, Pavel Makhnovskii, Oksana Tyapkina, Islam Nigmetzyanov, Leniz Nurullin, Ruslan Devyatiyarov, Elena Shagimardanova, Daniil Popov, and et al. 2021. "Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle" Biology 10, no. 6: 557. https://doi.org/10.3390/biology10060557