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Global Regulation of Promoter Melting in Naive Lymphocytes
Open accessAbstract
Lymphocyte activation is initiated by a global increase in messenger RNA synthesis. However, the mechanisms driving transcriptome amplification during the immune response are unknown. By monitoring single-stranded DNA genome wide, we show that the genome of naive cells is poised for rapid activation. In G0, ∼90% of promoters from genes to be expressed in cycling lymphocytes are polymerase loaded but unmelted and support only basal transcription. Furthermore, the transition from abortive to productive elongation is kinetically limiting, causing polymerases to accumulate nearer to transcription start sites. Resting lymphocytes also limit the expression of the transcription factor IIH complex, including XPB and XPD helicases involved in promoter melting and open complex extension. To date, two rate-limiting steps have been shown to control global gene expression in eukaryotes: preinitiation complex assembly and polymerase pausing. Our studies identify promoter melting as a third key regulatory step and propose that this mechanism ensures a prompt lymphocyte response to invading pathogens.
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“Including exogenous reference transcripts (‘spike-ins’) is useful both for quality control [1, 197] and for library-size normalization [198].”
From A survey of best practices for RNA-seq data analysis (2016) · cites this paper as [198]
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Competitive superhelical transitions involving cruciform extrusion
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Coming to terms with chromatin structure
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Metadata
- Authors
- Kouzine, F., Wojtowicz, D., Yamane, A., Resch, W., Kieffer-Kwon, K.-R., Bandle, R., Nelson, S., Nakahashi, H., Awasthi, P., Feigenbaum, L., Menoni, H., Hoeijmakers, J., Vermeulen, W., Ge, H., Przytycka, T. M., Levens, D., & Casellas, R.
- Affiliations
- National Institutes of Health (US)
- Erasmus MC (NL)
- Corresponding author
- Levens, David
- Casellas, Rafael
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 153
- Issue
- 5
- Pages
- 988-999
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3684982
- OpenAlex
- W1991098988
- Cited by
- 154
- References
- 83
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 16 · 2021: 6 · 2020: 11 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 16 · 2015: 13 · 2014: 19 · 2013: 12
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Cancer Research Institute
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIAAR041149)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- promoter melting, naive lymphocytes, lymphocyte activation, transcriptional activation, RNA polymerase II, abortive transcription, TFIIH, XPB helicase, XPD helicase, single-stranded DNA, preinitiation complex, polymerase pausing
- MeSH terms
- Animals, B-Lymphocytes, DNA, Single-Stranded, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Lymphocyte Activation, Lymphocytes, Promoter Regions, Genetic, Transcription, Genetic, Cell Line, Tumor, Mice, Transcription Factor TFIIH, Genome-Wide Association Study
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