한빛사 논문
Chiyeol Choi1,2, Taehoon Kim1,2, Karen T Chang3 and Kyung‐Tai Min1,2,*
1 Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
2 National Creative Research Initiative Center for Proteostasis, Ulsan National Institute of Science and Technology, Ulsan, Korea
3 Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
*Corresponding author : Kyung‐Tai Min
Abstract
Whether epigenetic factors such as DNA methylation and microRNAs interact to control adult hippocampal neurogenesis is not fully understood. Here, we show that Down syndrome critical region 1 (DSCR1) protein plays a key role in adult hippocampal neurogenesis by modulating two epigenetic factors: TET1 and miR‐124. We find that DSCR1 mutant mice have impaired adult hippocampal neurogenesis. DSCR1 binds to TET1 introns to regulate splicing of TET1, thereby modulating TET1 level. Furthermore, TET1 controls the demethylation of the miRNA‐124 promoter to modulate miR‐124 expression. Correcting the level of TET1 in DSCR1 knockout mice is sufficient to prevent defective adult neurogenesis. Importantly, restoring DSCR1 level in a Down syndrome mouse model effectively rescued adult neurogenesis and learning and memory deficits. Our study reveals that DSCR1 plays a critical upstream role in epigenetic regulation of adult neurogenesis and provides insights into potential therapeutic strategy for treating cognitive defects in Down syndrome.
Keywords : adult hippocampal neurogenesis; Down syndrome; DSCR1; TET1; miR-124
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