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Data from: Transcriptional regulation of human NMNAT2: Insights from 3D genome sequencing and bioinformatics

Chang, Yu Chen1; Yang, Sen1; Cho, Minyoung2; Nho, Kwangsik2; Baizabal, José-Manuel1; Lu, Hui-Chen1

Published Dec 12, 2025 on Dryad. https://doi.org/10.5061/dryad.rv15dv4kg

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Dec 12, 2025 version files 1.20 MB

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Abstract

Nicotinamide mononucleotide adenylyl transferases 2 (NMNAT2) is a crucial enzyme involved in the synthesis of nicotinamide adenine dinucleotide (NAD), which is vital for neuronal health. NMNAT2 mRNA levels positively correlate with cognitive function in older adults but decline following various injuries or proteinopathies. To explore the transcriptional regulation of NMNAT2, we employed chromosome conformation capture followed by high-throughput sequencing (4C-seq) to identify potential enhancer and silencer regions interacting with the NMNAT2 promoter. Our findings revealed distinct NMNAT2 promoter interactomes in undifferentiated versus neuron-like SH-SY5Y cells. Through bioinformatics analyses—including the Genomic Regions Enrichment of Annotations Tool (GREAT), MEME Suite, WhichTF, FIMO, and RNA sequencing—we pinpointed potential NMNAT2-associated genes and transcription factors. Using data from the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) single-nucleus RNA sequencing, we demonstrated that the expression levels of many NMNAT2-associated genes significantly correlate with NMNAT2 in human neurons. Employing CRISPR-Cas9 strategies, we confirmed the necessity of two specific genomic regions within the interactomes and four transcription factors for regulating NMNAT2 transcription. Together, our study identifies distinctive genomic loci containing NMNAT2 regulatory elements in undifferentiated versus neuron-like SH-SY5Y cells, as well as NMNAT2-associated genes and putative transcription factors.