Epigenetics communications最新文献

{"title":"Transcription bursting and epigenetic plasticity: an updated view","authors":"W. Beckman, M. Jiménez, P. J. Verschure","doi":"10.1186/s43682-021-00007-1","DOIUrl":"https://doi.org/10.1186/s43682-021-00007-1","url":null,"abstract":"","PeriodicalId":72947,"journal":{"name":"Epigenetics communications","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41932187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics Communications: where are we?","authors":"L. Altucci, M. Rots","doi":"10.1186/s43682-021-00006-2","DOIUrl":"https://doi.org/10.1186/s43682-021-00006-2","url":null,"abstract":"","PeriodicalId":72947,"journal":{"name":"Epigenetics communications","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47785055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients","authors":"Dongjing Liu, Annie I. Arockiaraj, J. Shaffer, S. Poloyac, P. Sherwood, S. Alexander, E. Crago, D. Weeks, Y. Conley","doi":"10.1186/s43682-021-00001-7","DOIUrl":"https://doi.org/10.1186/s43682-021-00001-7","url":null,"abstract":"","PeriodicalId":72947,"journal":{"name":"Epigenetics communications","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44135792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage.","authors":"Lacey W Heinsberg, Daniel E Weeks, Sheila A Alexander, Ryan L Minster, Paula R Sherwood, Samuel M Poloyac, Sandra Deslouches, Elizabeth A Crago, Yvette P Conley","doi":"10.1186/s43682-021-00003-5","DOIUrl":"10.1186/s43682-021-00003-5","url":null,"abstract":"<p><strong>Background: </strong>Following aneurysmal subarachnoid hemorrhage (aSAH), the brain is susceptible to ferroptosis, a type of iron-dependent cell death. Therapeutic intervention targeting the iron homeostasis pathway shows promise for mitigating ferroptosis and improving recovery in animal models, but little work has been conducted in humans. DNA methylation (DNAm) plays a key role in gene expression and brain function, plasticity, and injury recovery, making it a potentially useful biomarker of outcomes or therapeutic target for intervention. Therefore, in this longitudinal, observational study, we examined the relationships between trajectories of DNAm in candidate genes related to iron homeostasis and acute (cerebral vasospasm and delayed cerebral ischemia) and long-term (Glasgow Outcome Scale [GOS, unfavorable = 1-3] and death) patient outcomes after aSAH.</p><p><strong>Results: </strong>Longitudinal, genome-wide DNAm data were generated from DNA extracted from post-aSAH cerebrospinal fluid (<i>n</i> = 260 participants). DNAm trajectories of 637 CpG sites in 36 candidate genes related to iron homeostasis were characterized over 13 days post-aSAH using group-based trajectory analysis, an unsupervised clustering method. Significant associations were identified between inferred DNAm trajectory groups at several CpG sites and acute and long-term outcomes. Among our results, cg25713625 in the STEAP3 metalloreductase gene (<i>STEAP3</i>) stood out. Specifically, in comparing the highest cg25713625 DNAm trajectory group with the lowest, we observed significant associations (i.e., based on <i>p</i>-values less than an empirical significance threshold) with unfavorable GOS at 3 and 12 months (<i>OR</i> = 11.7, <i>p</i> = 0.0006 and <i>OR</i> = 15.6, <i>p</i> = 0.0018, respectively) and death at 3 and 12 months (<i>OR</i> = 19.1, <i>p</i> = 0.0093 and <i>OR</i> = 12.8, <i>p</i> = 0.0041, respectively). These results were replicated in an independent sample (<i>n</i> = 100 participants) observing significant associations with GOS at 3 and 12 months (<i>OR</i> = 8.2, <i>p</i> = 0.001 and <i>OR</i> = 6.3, <i>p</i> = 0.0.0047, respectively) and death at 3 months (<i>OR</i> = 2.3, <i>p</i> = 0.008) and a suggestive association (i.e., <i>p</i>-value < 0.05 not meeting an empirical significance threshold) with death at 12 months (<i>OR</i> = 2.0, <i>p</i> = 0.0272). In both samples, an additive effect of the DNAm trajectory group was observed as the percentage of participants with unfavorable long-term outcomes increased substantially with higher DNAm trajectory groups.</p><p><strong>Conclusion: </strong>Our results support a role for DNAm of cg25713625/<i>STEAP3</i> in recovery following aSAH. Additional research is needed to further explore the role of DNAm of cg25713625/<i>STEAP3</i> as a biomarker of unfavorable outcomes, or therapeutic target to improve outcomes, to translate these findings clinically.</p>","PeriodicalId":72947,"journal":{"name":"Epigenetics communications","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39863051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of cerebrospinal fluid DNA methylation age during the acute recovery period following aneurysmal subarachnoid hemorrhage.","authors":"Lacey W Heinsberg,&nbsp;Dongjing Liu,&nbsp;John R Shaffer,&nbsp;Daniel E Weeks,&nbsp;Yvette P Conley","doi":"10.1186/s43682-021-00002-6","DOIUrl":"https://doi.org/10.1186/s43682-021-00002-6","url":null,"abstract":"<p><strong>Background: </strong>Biological aging may occur at different rates than chronological aging due to genetic, social, and environmental factors. DNA methylation (DNAm) age is thought to be a reliable measure of accelerated biological aging which has been linked to an array of poor health outcomes. Given the importance of chronological age in recovery following aneurysmal subarachnoid hemorrhage (aSAH), a type of stroke, DNAm age may also be an important biomarker of outcomes, further improving predictive models. Cerebrospinal fluid (CSF) is a unique tissue representing the local central nervous system environment post-aSAH. However, the validity of CSF DNAm age is unknown, and it is unclear which epigenetic clock is ideal to compute CSF DNAm age, particularly given changes in cell type heterogeneity (CTH) during the acute recovery period. Further, the stability of DNAm age post-aSAH, specifically, has not been examined and may improve our understanding of patient recovery post-aSAH. Therefore, the purpose of this study was to characterize CSF DNAm age over 14 days post-aSAH using four epigenetic clocks.</p><p><strong>Results: </strong>Genome-wide DNAm data were available for two tissues: (1) CSF for <i>N</i> = 273 participants with serial sampling over 14 days post-aSAH (<i>N =</i> 850 samples) and (2) blood for a subset of <i>n</i> = 72 participants at one time point post-aSAH. DNAm age was calculated using the Horvath, Hannum, Levine, and \"Improved Precision\" (Zhang) epigenetic clocks. \"Age acceleration\" was computed as the residuals of DNAm age regressed on chronological age both with and without correcting for CTH. Using scatterplots, Pearson correlations, and group-based trajectory analysis, we examined the relationships between CSF DNAm age and chronological age, the concordance between DNAm ages calculated from CSF versus blood, and the stability (i.e., trajectories) of CSF DNAm age acceleration over time during recovery from aSAH. We observed moderate to strong correlations between CSF DNAm age and chronological age (<i>R</i> = 0.66 [Levine] to <i>R</i> = 0.97 [Zhang]), moderate to strong correlations between DNAm age in CSF versus blood (<i>R</i> = 0.69 [Levine] to <i>R</i> = 0.98 [Zhang]), and stable CSF age acceleration trajectories over 14 days post-aSAH in the Horvath and Zhang clocks (unadjusted for CTH), as well as the Hannum clock (adjusted for CTH).</p><p><strong>Conclusions: </strong>CSF DNAm age was generally stable post-aSAH. Although correlated, CSF DNAm age differs from blood DNAm age in the Horvath, Hannum, and Levine clocks, but not in the Zhang clock. Taken together, our results suggest that, of the clocks examined here, the Zhang clock is the most robust to CTH and is recommended for use in complex tissues such as CSF.</p>","PeriodicalId":72947,"journal":{"name":"Epigenetics communications","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39863050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}