|The CCAAT-box transcription factor, NF-Y complex, mediates neuronal specification of the IL1 neurons in C. elegans
|Woojung Heo1 (Graduate student), Hyeonjeong Hwang1 (Graduate student), Jimin Kim1 (Graduate student), SeungHee Oh1 (Graduate student), Youngseok Yu2 (Graduate student), Jae-Hyung Lee1 (Professor), Kyuhyung Kim 1,* (Professor)
|1Brain Sciences, DGIST,
2Life and Nanopharmaceutical Sciences and 3Oral Microbiology, Kyung Hee University
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.
|Abstract, Accepted Manuscript(in press) [Submitted on September 16, 2022, Accepted on October 27, 2022]