KMID : 0578320180410070695
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Molecules and Cells 2018 Volume.41 No. 7 p.695 ~ p.702
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CTCF Regulates Otic Neurogenesis via Histone Modification in the Neurog1 Locus
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Shin Jeong-Oh
Lee Jong-Joo Kim Mi-Kyoung Chung Youn-Wook Min Hye-Hyun Kim Jae-Yoon Kim Hyoung-Pyo Bok Jin-Woong
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Abstract
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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 Ctcf knockout mouse embryos (Pax2-Cre; Ctcffl/fl). The loss of Ctcf resulted in multiple defects of inner ear development and severely compromised otic neurogenesis, which was partly due to a loss of Neurog1 expression. Furthermore, reduced Neurog1 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 Neurog1 locus.
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KEYWORD
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CTCF, inner ear development, neurogenesis, Neurog1
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