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.

中文翻译：

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胚胎组织分化的特点是细胞周期动态相关核心启动子调控的转变。

核心启动子是转录起始位点 (TSS) 周围的一段 DNA，是控制基因转录的调节信号的主要整合点。细胞分化的特点是不同命运的细胞之间转录库和细胞周期行为的差异。启动子相关基因调控网络在细胞周期动力学发育相关转变中的作用知之甚少。这项研究在脊椎动物胚胎中展示了核心启动子变异如何定义细胞从增殖表型转变为细胞谱系特定表型的转录输出。使用 FUCCI 转基因细胞周期阶段标记评估斑马鱼胚胎分割中的细胞增殖，揭示了细胞周期行为中的空间和谱系特异性分离。为了研究差异启动子使用在该过程中的作用，对通过循环动力学分离的细胞进行基因表达帽分析 (CAGE)。该分析显示组织特异性基因表达显着增加，同时循环行为减慢。我们发现，除了 Sp1 结合位点之外，在缓慢循环、分化组织中上调的基因中 TSS 利用率明显提高，这与 TATA 盒的利用率提高有关。相反，在快速循环细胞中上调的基因携带广泛分布的 TSS 利用率，以及 CCAAT 盒的富集。这些启动子特征似乎对应于细胞周期动态而不是组织/细胞谱系起源。而且，我们观察到在 TSS 分布和替代启动子的差异利用中具有细胞周期动态相关转换的基因。这些结果证明了核心启动子在胚胎发育过程中在细胞周期依赖性转录调节中的调节作用。