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.

激活转录因子 5 (ATF5) 是一种转录因子，属于 cAMP 反应元件结合蛋白/ATF 家族，对于小鼠嗅觉器官中感觉神经元的分化和存活至关重要。然而，ATF5 的转录靶基因尚未确定。本研究通过染色质免疫沉淀-定量聚合酶链反应（ChIP-qPCR）实验来验证出生后幼犬主要嗅上皮和犁鼻器中 ATF5 靶基因。使用血凝素 (HA) 标记的 ATF5 敲入嗅觉器官进行 ChIP-qPCR。获得的结果表明，ATF5-HA融合蛋白与新生螺旋-环-螺旋1（Nhlh1）增强子区域的CCAAT/增强子结合蛋白-ATF反应元件（CARE）位点结合，Nhlh1是一种在分化嗅觉中表达的转录因子。和犁鼻感觉神经元。^{Nhlh1 mRNA 表达在 ATF5 缺陷 (ATF5 −/−} ) 嗅觉器官中下调。LIM/同源盒蛋白转录因子 Lhx2 与 ATF5 共定位于嗅觉和犁鼻感觉神经元的细胞核中，并与 Nhlh1 基因中 CARE 位点附近的同源域位点结合。Nhlh1 基因的 CARE 区域被活性增强子标记乙酰基组蛋白 H3 (Lys27) 富集。本研究确定 Nhlh1 是小鼠嗅觉器官中 ATF5 的新靶基因。ATF5 可能与 Lhx2 一起上调 Nhlh1 的表达，从而促进嗅觉和犁鼻感觉神经元的分化。