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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans

  • Woojung Heo (Department of Brain Sciences, DGIST) ;
  • Hyeonjeong Hwang (Department of Brain Sciences, DGIST) ;
  • Jimin Kim (Department of Brain Sciences, DGIST) ;
  • Seung Hee Oh (Department of Brain Sciences, DGIST) ;
  • Youngseok Yu (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Jae-Hyung Lee (Department of Life and Nanopharmaceutical Sciences, Kyung Hee University) ;
  • Kyuhyung Kim (Department of Brain Sciences, DGIST)
  • 투고 : 2022.09.16
  • 심사 : 2022.10.27
  • 발행 : 2023.03.31
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초록

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between trans-acting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cis-regulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.

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과제정보

We thank the Caenorhabditis Genetics Center (NIH Office of Research Infrastructure Programs, P40 OD010440) and the National BioResource Project (Japan) for strains. We also thank Jinmahn Kim and Ji-Won Lee for technical supports and K. Kim lab members for helpful comments and discussion on the manuscript. This work was supported by the National Research Foundation of Korea (NRF-2020R1A4A1019436, NRF-2021R1A2C1008418) (K.K.) and (2022R1F1A1071248) (J.L.).

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