Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul 03722, Korea.
Mol Cells. 2018 Jul 31;41(7):695-702. doi: 10.14348/molcells.2018.0230. Epub 2018 Jul 11.
The inner ear is a complex sensory organ responsible for hearing and balance. Formation of the inner ear is dependent on tight regulation of spatial and temporal expression of genes that direct a series of developmental processes. Recently, epigenetic regulation has emerged as a crucial regulator of the development of various organs. However, what roles higher-order chromatin organization and its regulator molecules play in inner ear development are unclear. CCCTC-binding factor (CTCF) is a highly conserved 11-zinc finger protein that regulates the three-dimensional architecture of chromatin, and is involved in various gene regulation processes. To delineate the role of CTCF in inner ear development, the present study investigated inner ear-specific knockout mouse embryos ( ). The loss of resulted in multiple defects of inner ear development and severely compromised otic neurogenesis, which was partly due to a loss of expression. Furthermore, reduced gene expression by CTCF knockdown was found to be associated with changes in histone modification at the gene's promoter, as well as its upstream enhancer. The results of the present study demonstrate that CTCF plays an essential role in otic neurogenesis by modulating histone modification in the locus.
内耳是一个复杂的感觉器官，负责听觉和平衡。内耳的形成依赖于指导一系列发育过程的基因的空间和时间表达的紧密调节。最近，表观遗传调控已成为各种器官发育的关键调节剂。然而，高级染色质组织及其调节分子在内耳发育中的作用尚不清楚。结合因子（CTCF）是一种高度保守的 11 锌指蛋白，可调节染色质的三维结构，并参与各种基因调控过程。为了阐明 CTCF 在内耳发育中的作用，本研究利用内耳特异性敲除小鼠胚胎（）进行了研究。的缺失导致内耳发育的多种缺陷，并严重损害了耳神经发生，这部分是由于的表达丧失。此外，通过 CTCF 敲低发现减少的基因表达与基因启动子处的组蛋白修饰以及其上游增强子的变化有关。本研究的结果表明，CTCF 通过调节 基因座上的组蛋白修饰在内耳神经发生中发挥重要作用。
