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Cited by 180Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Two independent transcription initiation codes overlap on vertebrate core promoters

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Haberle, Vanja, Li, Nan, Hadzhiev, Yavor, Plessy, Charles, Previti, Christopher, Nepal, Chirag, Gehrig, Jochen, Dong, Xianjun +9 more·2014·Nature
DOI 10.1038/nature12974PMC PMC4820030
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Abstract

A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition. This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression, and determined the positions of H3K4me3-marked promoter-associated nucleosomes. Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (+1) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts.

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Authors
Haberle, V., Li, N., Hadzhiev, Y., Plessy, C., Previti, C., Nepal, C., Gehrig, J., Dong, X., Akalin, A., Suzuki, A. M., van IJcken, W. F. J., Armant, O., Ferg, M., Strähle, U., Carninci, P., Müller, F., & Lenhard, B.
Affiliations
  • Hammersmith Hospital (GB)
  • University of Birmingham (GB)
  • RIKEN (JP)
  • University of Bergen (NO)
  • Karlsruhe Institute of Technology (DE)
Corresponding author
  • Carninci, Piero
  • Müller, Ferenc
  • Lenhard, Boris
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2014-02-16
Volume
507
Issue
7492
Pages
381-385
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature12974
PMC
PMC4820030
OpenAlex
W2077173342
Cited by
180
References
2
Citations by year
2026: 4 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 13 · 2021: 9 · 2020: 25 · 2019: 14 · 2018: 16 · 2017: 16 · 2016: 25 · 2015: 15 · 2014: 6
FWCI
8.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
transcription start sites, maternal-to-zygotic transition, core promoter, zebrafish, zygotic genome activation, midblastula transition, H3K4me3, nucleosome positioning, oocyte-to-embryo transition, RNA polymerase II
MeSH terms
Animals, Base Sequence, Embryo, Nonmammalian, Female, Histones, Methylation, Mothers, Nucleosomes, Promoter Regions, Genetic, Zebrafish, Zygote, Gene Expression Regulation, Developmental, Transcription Initiation Site, Transcriptome, Transcription Initiation, Genetic

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