Ludwig-Maximilians-Universität München, Department Biochemie, Genzentrum, 81377 München, Germany.
Ludwig-Maximilians Universität München, Fakultät für Biologie, Biozentrum, 82152 Planegg-Martinsried, Germany.
Genome Res. 2019 May;29(5):771-783. doi: 10.1101/gr.242362.118. Epub 2019 Apr 8.
Establishment of spatial coordinates during embryogenesis relies on differential regulatory activity of axis patterning enhancers. Concentration gradients of activator and repressor transcription factors (TFs) provide positional information to each enhancer, which in turn promotes transcription of a target gene in a specific spatial pattern. However, the interplay between an enhancer regulatory activity and its accessibility as determined by local chromatin organization is not well understood. We profiled chromatin accessibility with ATAC-seq in narrow, genetically tagged domains along the antero-posterior axis in the blastoderm. We demonstrate that one-quarter of the accessible genome displays significant regional variation in its ATAC-seq signal immediately after zygotic genome activation. Axis patterning enhancers are enriched among the most variable intervals, and their accessibility changes correlate with their regulatory activity. In an embryonic domain where an enhancer receives a net activating TF input and promotes transcription, it displays elevated accessibility in comparison to a domain where it receives a net repressive input. We propose that differential accessibility is a signature of patterning -regulatory elements in the blastoderm and discuss potential mechanisms by which accessibility of enhancers may be modulated by activator and repressor TFs.
胚胎发生过程中的空间坐标的建立依赖于轴模式增强子的差异调控活性。激活剂和抑制剂转录因子 (TF) 的浓度梯度为每个增强子提供位置信息，从而促进特定空间模式下靶基因的转录。然而，增强子调控活性与其局部染色质组织确定的可及性之间的相互作用还不是很清楚。我们使用 ATAC-seq 在原肠胚的前后轴上的窄遗传标记区域中对染色质可及性进行了分析。我们证明，在合子基因组激活后立即，四分之一的可及基因组的 ATAC-seq 信号显示出显著的区域变化。轴模式增强子在最可变的间隔中富集，并且它们的可及性变化与其调控活性相关。在一个增强子接收到净激活 TF 输入并促进转录的胚胎域中，它的可及性与接收到净抑制输入的域相比升高。我们提出，差异可及性是原肠胚中模式-调节元件的特征，并讨论了激活剂和抑制剂 TF 可能调节增强子可及性的潜在机制。
