ArticleThe Journal of biological chemistry2013
Epigenetic switching by the metabolism-sensing factors in the generation of orexin neurons from mouse embryonic stem cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- Protein Acylation Modifications in Sleep Disorders: Mechanisms and Therapeutic Potential.Journal of molecular neuroscience : MN · 2026Review
- O-GlcNAcylation on serine 40 of histone H2A promotes proliferation and invasion in triple-negative breast cancer.Scientific reports · 2025Article
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation.Nutrients · 2024Review
- Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein & cell · 2022Review
- Valuing the Diversity of Research Methods to Advance Nutrition Science.Advances in nutrition (Bethesda, Md.) · 2022Article
- O-GlcNAcylation links oncogenic signals and cancer epigenetics.Discover oncology · 2021Review
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- Regulation of Nuclear Factor-kappaB Function byFrontiers in cell and developmental biology · 2021Review
- Roles of ten-eleven translocation family proteins and their O-linked β-N-acetylglucosaminylated forms in cancer development.Oncology letters · 2021Review
- Establishment of macaque trophoblast stem cell lines derived from cynomolgus monkey blastocysts.Scientific reports · 2020Article
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- Kynurenine, 3-OH-kynurenine, and anthranilate are nutrient metabolites that alter H3K4 trimethylation and H2AS40 O-GlcNAcylation at hypothalamus-related loci.Scientific reports · 2019Article
- Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Regulation of Brain DNA Methylation Factors and of the Orexinergic System by Cocaine and Food Self-Administration.Molecular neurobiology · 2019Article
- Involvement of PLAGL1/ZAC1 in hypocretin/orexin transcription.International journal of molecular medicine · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The orexin system plays a central role in the integration of sleep/wake and feeding behaviors in a broad spectrum of neural-metabolic physiology. Orexin-A and orexin-B are produced by the cleavage of prepro-orexin, which is encoded on the Hcrt gene. To date, methods for generating other peptide neurons could not induce orexin neurons from pluripotent stem cells. Considering that the metabolic status affects orexin expression, we supplemented the culture medium with a nutrient factor, ManNAc, and succeeded in generating functional orexin neurons from mouse ES cells. Because DNA methylation inhibitors and histone deacetylase inhibitors could induce Hcrt expression in mouse ES cells, the epigenetic mechanism may be involved in this orexin neurogenesis. DNA methylation analysis showed the presence of a tissue-dependent differentially methylated region (T-DMR) around the transcription start site of the Hcrt gene. In the orexin neurons induced by supplementation of ManNAc, the T-DMR of the Hcrt gene was hypomethylated in association with higher H3/H4 acetylation. Concomitantly, the histone acetyltransferases p300, CREB-binding protein (CBP), and Mgea5 (also called O-GlcNAcase) were localized to the T-DMR in the orexin neurons. In non-orexin-expressing cells, H3/H4 hypoacetylation and hyper-O-GlcNAc modification were observed at the T-DMRs occupied by O-GlcNAc transferase and Sirt1. Therefore, the results of the present study suggest that the glucose metabolite, ManNAc, induces switching from the inactive state by Ogt-Sirt1 to the active state by Mgea5, p300, and CBP at the Hcrt gene locus.
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