Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Elife. 2018 May 29;7:e37084. doi: 10.7554/eLife.37084.
CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.
CpG 岛是与大多数哺乳动物启动子相关的基因调控元件，但它们如何调节基因表达仍知之甚少。在这里，我们鉴定出 FBXL19 是小鼠胚胎干细胞 (ES) 中的 CpG 岛结合蛋白，并表明它与 CDK-Mediator 复合物相关联。我们发现 FBXL19 将 CDK-Mediator 募集到非转录发育基因的 CpG 岛相关启动子上，以在细胞谱系决定时为这些基因的激活做好准备。我们进一步表明，FBXL19 对 CpG 岛的识别对于小鼠的发育是必不可少的。总的来说，这揭示了一种新的以 CpG 岛为中心的机制，用于 CDK-Mediator 在 ES 细胞中募集到发育基因启动子上，并揭示了 CDK-Mediator 在细胞谱系决定时为这些发育基因的激活做好准备的必要性。
