論文 - 詳細
| RRC ID | 70329 |
|---|---|
| 著者 | Wragg JW, Roos L, Vucenovic D, Cvetesic N, Lenhard B, Müller F. |
| タイトル | Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation. |
| ジャーナル | 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. |
| 巻・号 | 48(15) |
| ページ | 8374-8392 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 19 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(EF1α:mKO2-zCdt1(1/190))rw0405b Tg(EF1α:mAG-zGem(1/100))rw0410h |