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Nescient helix-loop-helix 1 (Nhlh1) is a novel activating transcription factor 5 (ATF5) target gene in olfactory and vomeronasal sensory neurons in mice

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A Correction to this article was published on 26 March 2024

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Abstract

Activating transcription factor 5 (ATF5) is a transcription factor that belongs to the cAMP-response element-binding protein/ATF family and is essential for the differentiation and survival of sensory neurons in mouse olfactory organs. However, transcriptional target genes for ATF5 have yet to be identified. In the present study, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) experiments were performed to verify ATF5 target genes in the main olfactory epithelium and vomeronasal organ in the postnatal pups. ChIP-qPCR was conducted using hemagglutinin (HA)-tagged ATF5 knock-in olfactory organs. The results obtained demonstrated that ATF5-HA fusion proteins bound to the CCAAT/enhancer-binding protein-ATF response element (CARE) site in the enhancer region of nescient helix-loop-helix 1 (Nhlh1), a transcription factor expressed in differentiating olfactory and vomeronasal sensory neurons. Nhlh1 mRNA expression was downregulated in ATF5-deficient (ATF5−/−) olfactory organs. The LIM/homeobox protein transcription factor Lhx2 co-localized with ATF5 in the nuclei of olfactory and vomeronasal sensory neurons and bound to the homeodomain site proximal to the CARE site in the Nhlh1 gene. The CARE region of the Nhlh1 gene was enriched by the active enhancer marker, acetyl-histone H3 (Lys27). The present study identified Nhlh1 as a novel target gene for ATF5 in murine olfactory organs. ATF5 may upregulate Nhlh1 expression in concert with Lhx2, thereby promoting the differentiation of olfactory and vomeronasal sensory neurons.

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Data availability

The datasets generated and/or analyzed in the present study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to the members of Yuji Takahashi’s lab for their support on this project.

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Authors and Affiliations

  1. Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan

    Chiharu Ishii, Haruo Nakano, Riko Higashiseto, Yusaku Ooki, Mariko Umemura, Shigeru Takahashi & Yuji Takahashi

Authors
  1. Chiharu Ishii
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  2. Haruo Nakano
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  3. Riko Higashiseto
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  4. Yusaku Ooki
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  5. Mariko Umemura
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  6. Shigeru Takahashi
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  7. Yuji Takahashi
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Contributions

HN conceived the study and designed the project with CI, ST, and YT. MU maintained the ATF5-knockout mouse line. CI, HN, RH, and YO performed the experiments and analyzed the data. CI and HN wrote the manuscript, and all authors approved the final version of the manuscript.

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Correspondence to Haruo Nakano.

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All mouse studies were approved by the Institutional Animal Experiment Committee of the university and were performed in accordance with institutional and governmental guidelines.

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The original online version of this article was revised: The authors regret that the version of the supplementary file that appears in the original article is incorrect. The correct supplementary figure is provided in the erratum article. The original article has been corrected.

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Ishii, C., Nakano, H., Higashiseto, R. et al. Nescient helix-loop-helix 1 (Nhlh1) is a novel activating transcription factor 5 (ATF5) target gene in olfactory and vomeronasal sensory neurons in mice. Cell Tissue Res 396, 85–94 (2024). https://doi.org/10.1007/s00441-024-03871-0

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