ZFIN ID: ZDB-PUB-200704-17
Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation
Wragg, J.W., Roos, L., Vucenovic, D., Cvetesic, N., Lenhard, B., Müller, F.
Date: 2020
Source: Nucleic acids research   48(15): 8374-8392 (Journal)
Registered Authors: Müller, Ferenc
Keywords: none
MeSH Terms:
  • Animals
  • Binding Sites/genetics
  • Cell Cycle/genetics
  • Cell Differentiation/genetics
  • Cell Proliferation/genetics
  • Embryonic Development/genetics
  • Gene Regulatory Networks/genetics*
  • Humans
  • Morphogenesis/genetics
  • Promoter Regions, Genetic/genetics*
  • Sp1 Transcription Factor/genetics
  • TATA Box/genetics
  • Transcription Initiation Site*
  • Transcription, Genetic*
  • Zebrafish/genetics
PubMed: 32619237 Full text @ Nucleic Acids Res.
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.