Hes2, a mammalian basic helix-loop-helix transcriptional repressor, is homologous to the products of Drosophila hairy and Enhancer of split. It belongs to the Hes family of genes, which are involved in cell fate determination of stem cells (or precursor cells) by suppressing the expression of tissue-specific transcriptional activators. The activation of the Notch signaling pathway can lead to the transcriptional activation of Hes family genes, and Hes2 is one of them [1,2].

In mouse studies, the Hes2 gene was found to consist of four exons, and its introns are located within the protein-coding region at positions homologous to those of other Hes genes. It is mapped to the distal region of Chromosome 4 near the Hes3 and Hes5 loci. Transient transfection analyses demonstrated that, unlike Hes1 and Hes5, Hes2 promoter activities are not significantly upregulated by the active form of Notch, suggesting that Hes genes can be functionally classified into two groups based on Notch-regulation [2]. In infant mice, in-situ expression of BSH decreased markers of cell proliferation including Hes2, which may be related to microbial influence on gastrointestinal maturation [3]. In a study on the association between Notch signaling pathway polymorphisms and lung cancer risk, the HES2 rs11364 polymorphism was significantly associated with susceptibility to lung cancer [4].

In conclusion, Hes2 plays a role in cell fate determination related to stem cells and is associated with the Notch signaling pathway. Mouse models have provided insights into its gene structure and regulation differences compared to other Hes genes. Its association with gastrointestinal maturation in mice and lung cancer susceptibility in humans indicates its importance in both normal development and disease-related processes.

References:

1. Katoh, Masuko, Katoh, Masaru. . Identification and characterization of human HES2, HES3, and HES5 genes in silico. In International journal of oncology, 25, 529-34. doi:. https://pubmed.ncbi.nlm.nih.gov/15254753/

2. Nishimura, M, Isaka, F, Ishibashi, M, Nakanishi, S, Kageyama, R. . Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split. In Genomics, 49, 69-75. doi:. https://pubmed.ncbi.nlm.nih.gov/9570950/

3. Núñez-Sánchez, María A, Herisson, Florence M, Keane, Jonathan M, Caplice, Noel M, Gahan, Cormac G M. . Microbial bile salt hydrolase activity influences gene expression profiles and gastrointestinal maturation in infant mice. In Gut microbes, 14, 2149023. doi:10.1080/19490976.2022.2149023. https://pubmed.ncbi.nlm.nih.gov/36420990/

4. Xu, Q P, Xiao, R D, Xiong, W M, He, F, Cai, L. . [Association between polymorphism in notch signaling pathway and lung cancer risk]. In Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine], 52, 243-252. doi:10.3760/cma.j.issn.0253-9624.2018.03.006. https://pubmed.ncbi.nlm.nih.gov/29973002/