PUBLICATION

Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation

Authors
Wragg, J.W., Roos, L., Vucenovic, D., Cvetesic, N., Lenhard, B., Müller, F.
ID
ZDB-PUB-200704-17
Date
2020
Source
Nucleic acids research   48(15): 8374-8392 (Journal)
Registered Authors
Müller, Ferenc
Keywords
none
MeSH Terms
  • Cell Cycle/genetics
  • Gene Regulatory Networks/genetics*
  • Zebrafish/genetics
  • Cell Proliferation/genetics
  • Humans
  • Promoter Regions, Genetic/genetics*
  • Binding Sites/genetics
  • Morphogenesis/genetics
  • Transcription Initiation Site*
  • Animals
  • TATA Box/genetics
  • Sp1 Transcription Factor/genetics
  • Embryonic Development/genetics
  • Cell Differentiation/genetics
  • Transcription, Genetic*
(all 15)
PubMed
32619237 Full text @ Nucleic Acids Res.
Abstract
The core-promoter, a stretch of DNA surrounding the transcription start site (TSS), is a major integration-point for regulatory-signals controlling gene-transcription. Cellular differentiation is marked by divergence in transcriptional repertoire and cell-cycling behaviour between cells of different fates. The role promoter-associated gene-regulatory-networks play in development-associated transitions in cell-cycle-dynamics is poorly understood. This study demonstrates in a vertebrate embryo, how core-promoter variations define transcriptional output in cells transitioning from a proliferative to cell-lineage specifying phenotype. Assessment of cell proliferation across zebrafish embryo segmentation, using the FUCCI transgenic cell-cycle-phase marker, revealed a spatial and lineage-specific separation in cell-cycling behaviour. To investigate the role differential promoter usage plays in this process, cap-analysis-of-gene-expression (CAGE) was performed on cells segregated by cycling dynamics. This analysis revealed a dramatic increase in tissue-specific gene expression, concurrent with slowed cycling behaviour. We revealed a distinct sharpening in TSS utilization in genes upregulated in slowly cycling, differentiating tissues, associated with enhanced utilization of the TATA-box, in addition to Sp1 binding-sites. In contrast, genes upregulated in rapidly cycling cells carry broad distribution of TSS utilization, coupled with enrichment for the CCAAT-box. These promoter features appear to correspond to cell-cycle-dynamic rather than tissue/cell-lineage origin. Moreover, we observed genes with cell-cycle-dynamic-associated transitioning in TSS distribution and differential utilization of alternative promoters. These results demonstrate the regulatory role of core-promoters in cell-cycle-dependent transcription regulation, during embryo-development.
Genes / Markers
Figures
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Expression
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Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rw0405bTgTransgenic Insertion
    rw0410bTgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      mAGFPEFGmAGFP
      mKOFP2EFGmKOFP2
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      Mapping
      No data available
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      Citation
      Wragg, J.W., Roos, L., Vucenovic, D., Cvetesic, N., Lenhard, B., Müller, F. (2020) Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation. Nucleic acids research. 48(15):8374-8392.