RRC ID 70329
Author Wragg JW, Roos L, Vucenovic D, Cvetesic N, Lenhard B, Müller F.
Title Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation.
Journal 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.
Volume 48(15)
Pages 8374-8392
Published 2020-9-4
DOI 10.1093/nar/gkaa563
PII 5867103
PMID 32619237
PMC PMC7470974
MeSH 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
IF 11.502
Zebrafish Tg(EF1α:mKO2-zCdt1(1/190))rw0405b Tg(EF1α:mAG-zGem(1/100))rw0410h