The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans

Abstract

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between transacting transcription factors and cis-regulatoryelements 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 cisregulatory 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.

A sex-specific switch in a single glial cell patterns the apical extracellular matrix

“…We chose to focus on nfya-1 because it showed the strongest phenotype. In C. elegans , loss of nfya-1 has previously been shown to affect vulva development, sensory neuron specification, and expression of specific cell fate transcription factors (Deng et al, 2007; Milton et al, 2013; Aklilu et al, 2022; Heo et al, 2022). NFYA-1/NFY-A is a subunit of the conserved, ubiquitously expressed trimeric repressor complex NF-Y/CBF.…”

Nuclear Factor-Y is a Pervasive Regulator of Neuronal Gene Expression

“…We found that NFYA-1 loss caused gene expression to be abolished in certain neurons, such as the PVQs, as also shown recently for the IL1 neurons. (Heo et al, 2022).…”

“…We found that NFYA-1 loss caused gene expression to be abolished in certain neurons, such as the PVQs, as also shown recently for the IL1 neurons. (Heo et al, 2022). However, the majority of neuronal genes analyzed showed ∼20-40% changes in gene expression.…”

PIEZO acts in an intestinal valve to regulate swallowing inC. elegans

“…In 10 min after transferring worms, fluorescence time lapse images were acquired using an Axio cam 208 color with 6.3X objective and ZEN software for 10 min duration. Images obtained at 0 min, 5min, and 10 min were analyzed using Image J 53 , and average fluorescence intensities were calculated by using GraphPad Prism.…”