한빛사논문
DGIST
Byung Su Ko1,7, Myeong Hoon Han1,7, Min Jee Kwon1,7, Dong Gon Cha2,7, Yuri Ji1, Eun Seo Park2, Min Jae Jeon1, Somi Kim3, Kyeongho Lee1,4, Yoon Ha Choi2,3, Jusung Lee2, Monica Torras-Llort5, Ki-Jun Yoon6, Hyosang Lee1,4, Jong Kyoung Kim2,3 and Sung Bae Lee1
1Department of Brain Sciences, DGIST, Daegu 42988, Republic of Korea.
2Department of New Biology, DGIST, Daegu 42988, Republic of Korea.
3Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
4Convergence Research Advanced Centre for Olfaction, DGIST, Daegu 42988, Republic of Korea.
5Institute of Molecular Biology of Barcelona, CSIC, Barcelona, Spain.
6Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
7These authors contributed equally: Byung Su Ko, Myeong Hoon Han, Min Jee Kwon, Dong Gon Cha.
Corresponding authors : Correspondence to Jong Kyoung Kim or Sung Bae Lee.
Abstract
Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.
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