ArticleMolecular systems biology2023
Transcription factor expression is the main determinant of variability in gene co-activity.
Article in Molecular systems biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 15 citations in OpenAlex.
- Interaction Between Enhancers and Promoters in Chicken Genome.International journal of molecular sciences · 2025Article
- Article
- Transcriptome data are insufficient to control false discoveries in regulatory network inference.Cell systems · 2024Article
- Non-coding variants impact cis-regulatory coordination in a cell type-specific manner.Genome biology · 2024Article
- Mapping the landscape of lineage-specific dynamic regulation of gene expression using single-cell transcriptomics and application to genetics of complex disease.medRxiv : the preprint server for health sciences · 2023Article
- Transcription factor expression is the main determinant of variability in gene co-activity.Molecular systems biology · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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