The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans
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Neuronal differentiation is highly coordinated through a cascadeof gene expression, mediated via interactions between transactingtranscription factors and cis-regulatory elements of theirtarget genes. However, the mechanisms of transcriptional regulationthat 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 expressthe flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but notventral IL1s of nfya-1 mutants. The expression of another terminallydifferentiated gene, eat-4 vesicular glutamate transporter,is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronalgenes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 andeat-4 expression. Ectopic expression of NFYA-1 drives the expressionof flp-3 gene in other cell-types. Promoter analysis ofIL1-expressed genes results in the identification of several cisregulatorymotifs which are necessary for IL1 expression, includinga putative CCAAT-box located in the flp-3 promoterthat NFYA-1 directly interacts with. NFYA-1 and NFYA-2, togetherwith NFYB-1 and NFYC-1, exhibit partly or fully redundantroles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Ycomplex regulates neuronal subtype-specification via regulatinga set of terminal-differentiation genes.
Abstract
Neuronal differentiation is highly coordinated through a cascadeof gene expression, mediated via interactions between transactingtranscription factors and cis-regulatory elements of theirtarget genes. However, the mechanisms of transcriptional regulationthat 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 expressthe flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but notventral IL1s of nfya-1 mutants. The expression of another terminallydifferentiated gene, eat-4 vesicular glutamate transporter,is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronalgenes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 andeat-4 expression. Ectopic expression of NFYA-1 drives the expressionof flp-3 gene in other cell-types. Promoter analysis ofIL1-expressed genes results in the identification of several cisregulatorymotifs which are necessary for IL1 expression, includinga putative CCAAT-box located in the flp-3 promoterthat NFYA-1 directly interacts with. NFYA-1 and NFYA-2, togetherwith NFYB-1 and NFYC-1, exhibit partly or fully redundantroles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Ycomplex regulates neuronal subtype-specification via regulatinga set of terminal-differentiation genes.
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