| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-123 |
Sentence |
denotes |
Epigenetic switching by the metabolism-sensing factors in the generation of orexin neurons from mouse embryonic stem cells. |
| T2 |
124-269 |
Sentence |
denotes |
The orexin system plays a central role in the integration of sleep/wake and feeding behaviors in a broad spectrum of neural-metabolic physiology. |
| T3 |
270-373 |
Sentence |
denotes |
Orexin-A and orexin-B are produced by the cleavage of prepro-orexin, which is encoded on the Hcrt gene. |
| T4 |
374-488 |
Sentence |
denotes |
To date, methods for generating other peptide neurons could not induce orexin neurons from pluripotent stem cells. |
| T5 |
489-695 |
Sentence |
denotes |
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. |
| T6 |
696-883 |
Sentence |
denotes |
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. |
| T7 |
884-1045 |
Sentence |
denotes |
DNA methylation analysis showed the presence of a tissue-dependent differentially methylated region (T-DMR) around the transcription start site of the Hcrt gene. |
| T8 |
1046-1197 |
Sentence |
denotes |
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. |
| T9 |
1198-1364 |
Sentence |
denotes |
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. |
| T10 |
1365-1522 |
Sentence |
denotes |
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. |
| T11 |
1523-1734 |
Sentence |
denotes |
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. |
