論文 - 詳細
| RRC ID | 51372 |
|---|---|
| 著者 | Huang H, Zhu Y, Eliot MN, Knopik VS, McGeary JE, Carskadon MA, Hart AC. |
| タイトル | Combining Human Epigenetics and Sleep Studies in Caenorhabditis elegans: A Cross-Species Approach for Finding Conserved Genes Regulating Sleep. |
| ジャーナル | Sleep |
| Abstract |
Study Objectives:We aimed to test a combined approach to identify conserved genes regulating sleep and to explore the association between DNA methylation and sleep length. Methods:We identified candidate genes associated with shorter versus longer sleep duration in college students based on DNA methylation using Illumina Infinium HumanMethylation450 BeadChip arrays. Orthologous genes in Caenorhabditis elegans were identified, and we examined whether their loss of function affected C. elegans sleep. For genes whose perturbation affected C. elegans sleep, we subsequently undertook a small pilot study to re-examine DNA methylation in an independent set of human participants with shorter versus longer sleep durations. Results:Eighty-seven out of 485,577 CpG sites had significant differential methylation in young adults with shorter versus longer sleep duration, corresponding to 52 candidate genes. We identified 34 C. elegans orthologs, including NPY/flp-18 and flp-21, which are known to affect sleep. Loss of five additional genes alters developmentally timed C. elegans sleep (B4GALT6/bre-4, DOCK180/ced-5, GNB2L1/rack-1, PTPRN2/ida-1, ZFYVE28/lst-2). For one of these genes, ZFYVE28 (also known as hLst2), the pilot replication study again found decreased DNA methylation associated with shorter sleep duration at the same two CpG sites in the first intron of ZFYVE28. Conclusions:Using an approach that combines human epigenetics and C. elegans sleep studies, we identified five genes that play previously unidentified roles in C. elegans sleep. We suggest sleep duration in humans may be associated with differential DNA methylation at specific sites and that the conserved genes identified here likely play roles in C. elegans sleep and in other species. |
| 巻・号 | 40(6) |
| 公開日 | 2017-6-1 |
| DOI | 10.1093/sleep/zsx063 |
| PII | 3738764 |
| PMID | 28431118 |
| PMC | PMC6075530 |
| MeSH | Adult Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Conserved Sequence* CpG Islands / genetics DNA Methylation / genetics* Epigenesis, Genetic* Female Glycosyltransferases Humans Male Membrane Glycoproteins Membrane Proteins Pilot Projects Protein Tyrosine Phosphatases Receptors, Cytoplasmic and Nuclear Sleep / genetics* Sleep / physiology* Sorting Nexins Time Factors Young Adult |
| IF | 4.805 |
| 引用数 | 4 |
| リソース情報 | |
| 線虫 | tm1949 tm2262 tm334 tm6929 |