Transcription factor expression is the main determinant of variability in gene co‐activity
Abstract Many genes are co‐expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants of domain co‐activity remain unclear. Here, we leverage human individual variation in gene expression to characterize the co‐regulatory processes underlying domain co‐acti...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-05-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202211392 |
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| author | Lucas van Duin Robert Krautz Sarah Rennie Robin Andersson |
| author_facet | Lucas van Duin Robert Krautz Sarah Rennie Robin Andersson |
| author_sort | Lucas van Duin |
| collection | DOAJ |
| description | Abstract Many genes are co‐expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants of domain co‐activity remain unclear. Here, we leverage human individual variation in gene expression to characterize the co‐regulatory processes underlying domain co‐activity and systematically quantify their effect sizes. We employ transcriptional decomposition to extract from RNA expression data an expression component related to co‐activity revealed by genomic positioning. This strategy reveals close to 1,500 co‐activity domains, covering most expressed genes, of which the large majority are invariable across individuals. Focusing specifically on domains with high variability in co‐activity reveals that contained genes have a higher sharing of eQTLs, a higher variability in enhancer interactions, and an enrichment of binding by variably expressed transcription factors, compared to genes within non‐variable domains. Through careful quantification of the relative contributions of regulatory processes underlying co‐activity, we find transcription factor expression levels to be the main determinant of gene co‐activity. Our results indicate that distal trans effects contribute more than local genetic variation to individual variation in co‐activity domains. |
| format | Article |
| id | doaj-art-c0ff0e72b3834be1a2a4a6dc42af6a37 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c0ff0e72b3834be1a2a4a6dc42af6a372024-11-10T12:48:18ZengSpringer NatureMolecular Systems Biology1744-42922023-05-0119711710.15252/msb.202211392Transcription factor expression is the main determinant of variability in gene co‐activityLucas van Duin0Robert Krautz1Sarah Rennie2Robin Andersson3Section for Computational and RNA Biology, Department of Biology, University of CopenhagenSection for Computational and RNA Biology, Department of Biology, University of CopenhagenSection for Computational and RNA Biology, Department of Biology, University of CopenhagenSection for Computational and RNA Biology, Department of Biology, University of CopenhagenAbstract Many genes are co‐expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants of domain co‐activity remain unclear. Here, we leverage human individual variation in gene expression to characterize the co‐regulatory processes underlying domain co‐activity and systematically quantify their effect sizes. We employ transcriptional decomposition to extract from RNA expression data an expression component related to co‐activity revealed by genomic positioning. This strategy reveals close to 1,500 co‐activity domains, covering most expressed genes, of which the large majority are invariable across individuals. Focusing specifically on domains with high variability in co‐activity reveals that contained genes have a higher sharing of eQTLs, a higher variability in enhancer interactions, and an enrichment of binding by variably expressed transcription factors, compared to genes within non‐variable domains. Through careful quantification of the relative contributions of regulatory processes underlying co‐activity, we find transcription factor expression levels to be the main determinant of gene co‐activity. Our results indicate that distal trans effects contribute more than local genetic variation to individual variation in co‐activity domains.https://doi.org/10.15252/msb.202211392co‐activity domainsco‐regulationgene regulationindividual variationtranscriptional decomposition |
| spellingShingle | Lucas van Duin Robert Krautz Sarah Rennie Robin Andersson Transcription factor expression is the main determinant of variability in gene co‐activity Molecular Systems Biology co‐activity domains co‐regulation gene regulation individual variation transcriptional decomposition |
| title | Transcription factor expression is the main determinant of variability in gene co‐activity |
| title_full | Transcription factor expression is the main determinant of variability in gene co‐activity |
| title_fullStr | Transcription factor expression is the main determinant of variability in gene co‐activity |
| title_full_unstemmed | Transcription factor expression is the main determinant of variability in gene co‐activity |
| title_short | Transcription factor expression is the main determinant of variability in gene co‐activity |
| title_sort | transcription factor expression is the main determinant of variability in gene co activity |
| topic | co‐activity domains co‐regulation gene regulation individual variation transcriptional decomposition |
| url | https://doi.org/10.15252/msb.202211392 |
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