Cited by 156Genomics and Chromatin DynamicsNuclear Structure and FunctionGene Regulatory Network Analysis

Global Regulation of Promoter Melting in Naive Lymphocytes

Open access
Kouzine, Fedor, Wojtowicz, Damian, Yamane, Arito, Resch, Wolfgang, Kieffer-Kwon, Kyong-Rim, Bandle, Russell, Nelson, Steevenson, Nakahashi, Hirotaka +9 more·2013·Cell

Abstract

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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Crossref · 10.1016/j.cell.2013.04.033

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  • Including exogenous reference transcripts (spike-ins) is useful for quality control and for library-size normalization.

    “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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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
Venue
Cell
Publisher
Elsevier BV
Published
2013-05
Volume
153
Issue
5
Pages
988-999
ISSN
0092-8674 (ISSN-L)
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
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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