Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome
Open accessAbstract
We present evidence that transcriptional activation of the human interferon-beta (IFN beta) gene requires the assembly of a higher order transcription enhancer complex (enhanceosome). This multicomponent complex includes at least three distinct transcription factors and the high mobility group protein HMG I(Y). Both the in vitro assembly and in vivo transcriptional activity of this complex require a precise helical relationship between individual transcription factor-binding sites. In addition, HMG I(Y), which binds specifically to three sites within the enhancer, promotes cooperative binding of transcriptional factors in vitro and is required for transcriptional synergy between these factors in vivo. Thus, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome.
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The recruited TFs directly or indirectly facilitate chromatin remodelling and recruitment of the basal transcriptional machinery at the promoter, thereby enhancing transcription.
“The recruited TFs directly or indirectly (e.g. via a co-activator) facilitate chromatin remodelling and recruitment of the basal transcriptional machinery at the promoter (Figure 1a), thereby enhancing transcription91.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [91]
Virtually every nucleotide of the interferon beta enhancer is evolutionarily conserved, likely because eight transcription factors cooperate to form a composite surface that recognises the entire sequence as one effective binding site.
“Virtually every nucleotide of the interferon beta enhancer is evolutionarily conserved; this is likely because the eight TFs cooperate to form a composite surface that recognises the entire sequence of the enhancer as one effective binding site [88, 89].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [88]
The enhanceosome model suggests that transcription factor binding sites must remain in the same order and orientation for the enhancer to work.
“At the rigid end, the “enhanceosome” model suggests that the TF binding sites must remain in the same order and orientation for the enhancer to work.”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [88]
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- Authors
- Thanos, D., & Maniatis, T.
- Affiliations
- Harvard University (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1995-12
- Volume
- 83
- Issue
- 7
- Pages
- 1091-1100
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1997767982
- Cited by
- 1,014
- References
- 2
- Citations by year
- 2026: 11 · 2025: 26 · 2024: 28 · 2023: 23 · 2022: 12 · 2021: 30 · 2020: 21 · 2019: 18 · 2018: 29 · 2017: 24 · 2016: 22 · 2015: 29 · 2014: 26 · 2013: 37 · 2012: 26
- FWCI
- 17.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI20642)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interferon-beta, enhanceosome, transcriptional activation, HMGA1, transcription factors, transcriptional synergy
- MeSH terms
- Animals, Binding Sites, Drosophila, Enhancer Elements, Genetic, HeLa Cells, High Mobility Group Proteins, Humans, Promoter Regions, Genetic, Sensitivity and Specificity, Transcription Factors, Transfection, Y Chromosome, Gene Expression Regulation, Viral, Interferon-beta
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