Neijts Roel, Amin Shilu, van Rooijen Carina, Tan Sander, Creyghton Menno P, de Laat Wouter, Deschamps Jacqueline
Hubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Genes Dev. 2016 Sep 1;30(17):1937-42. doi: 10.1101/gad.285767.116. Epub 2016 Sep 15.
Sequential 3'-to-5' activation of the Hox gene clusters in early embryos is a most fascinating issue in developmental biology. Neither the trigger nor the regulatory elements involved in the transcriptional initiation of the 3'-most Hox genes have been unraveled in any organism. We demonstrate that a series of enhancers, some of which are Wnt-dependent, is located within a HoxA 3' subtopologically associated domain (subTAD). This subTAD forms the structural basis for multiple layers of 3'-polarized features, including DNA accessibility and enhancer activation. Deletion of the cassette of Wnt-dependent enhancers proves its crucial role in initial transcription of HoxA at the 3' side of the cluster.
早期胚胎中Hox基因簇从3'端到5'端的顺序激活是发育生物学中一个极其引人入胜的问题。在任何生物体中，3'端最外侧Hox基因转录起始所涉及的触发因素和调控元件都尚未被揭示。我们证明，一系列增强子（其中一些依赖Wnt）位于HoxA 3'亚拓扑相关结构域（subTAD）内。这个subTAD构成了多层3'极化特征的结构基础，包括DNA可及性和增强子激活。删除依赖Wnt的增强子盒证明了其在基因簇3'端HoxA初始转录中的关键作用。
