Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, Princeton, United States.
Elife. 2017 Sep 11;6:e28275. doi: 10.7554/eLife.28275.
In , graded expression of the maternal transcription factor Bicoid (Bcd) provides positional information to activate target genes at different positions along the anterior-posterior axis. We have measured the genome-wide binding profile of Bcd using ChIP-seq in embryos expressing single, uniform levels of Bcd protein, and grouped Bcd-bound targets into four classes based on occupancy at different concentrations. By measuring the biochemical affinity of target enhancers in these classes in vitro and genome-wide chromatin accessibility by ATAC-seq, we found that the occupancy of target sequences by Bcd is not primarily determined by Bcd binding sites, but by chromatin context. Bcd drives an open chromatin state at a subset of its targets. Our data support a model where Bcd influences chromatin structure to gain access to concentration-sensitive targets at high concentrations, while concentration-insensitive targets are found in more accessible chromatin and are bound at low concentrations. This may be a common property of developmental transcription factors that must gain early access to their target enhancers while the chromatin state of the genome is being remodeled during large-scale transitions in the gene regulatory landscape.
在果蝇中，母体转录因子 Bicoid（Bcd）的分级表达为激活沿前后轴不同位置的靶基因提供了位置信息。我们使用 ChIP-seq 测量了在表达单一、均匀水平 Bcd 蛋白的胚胎中 Bcd 的全基因组结合谱，并根据在不同浓度下的占据情况将 Bcd 结合靶标分为四类。通过测量这些类别中靶增强子的体外生化亲和力和全基因组染色质可及性通过 ATAC-seq，我们发现靶序列的 Bcd 占据主要不是由 Bcd 结合位点决定的，而是由染色质环境决定的。Bcd 在其靶标的一部分上驱动开放染色质状态。我们的数据支持这样一种模型，即 Bcd 影响染色质结构，以便在高浓度时获得对浓度敏感的靶标，而浓度不敏感的靶标存在于更易接近的染色质中，并在低浓度时结合。这可能是发育转录因子的一个共同特性，它们必须在基因组的染色质状态在基因调控景观的大规模转变过程中重塑时，早期获得其靶增强子。
