Pub Date : 2015-01-01DOI: 10.1016/j.nepig.2014.10.004
Lisa H. Chadwick , Akira Sawa , Ivana V. Yang , Andrea Baccarelli , Xandra O. Breakefield , Hong-Wen Deng , Dana C. Dolinoy , M. Daniele Fallin , Nina T. Holland , E. Andres Houseman , Stavros Lomvardas , Mahendra Rao , John S. Satterlee , Frederick L. Tyson , Pandurangan Vijayanand , John M. Greally
Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field.
{"title":"New insights and updated guidelines for epigenome-wide association studies","authors":"Lisa H. Chadwick , Akira Sawa , Ivana V. Yang , Andrea Baccarelli , Xandra O. Breakefield , Hong-Wen Deng , Dana C. Dolinoy , M. Daniele Fallin , Nina T. Holland , E. Andres Houseman , Stavros Lomvardas , Mahendra Rao , John S. Satterlee , Frederick L. Tyson , Pandurangan Vijayanand , John M. Greally","doi":"10.1016/j.nepig.2014.10.004","DOIUrl":"10.1016/j.nepig.2014.10.004","url":null,"abstract":"<div><p>Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field.</p></div>","PeriodicalId":90931,"journal":{"name":"Neuroepigenetics","volume":"1 ","pages":"Pages 14-19"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nepig.2014.10.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55196204","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}
Pub Date : 2015-01-01DOI: 10.1016/j.nepig.2014.10.005
Alexi Nott , Sukhee Cho , Jinsoo Seo, Li-Huei Tsai
An experience-dependent postnatal increase in GABAergic inhibition in the visual cortex is important for the closure of a critical period of enhanced synaptic plasticity. Although maturation of the subclass of parvalbumin (Pv)–expressing GABAergic interneurons is known to contribute to critical period closure, the role of epigenetics on cortical inhibition and synaptic plasticity has not been explored. The transcription regulator, histone deacetylase 2 (HDAC2), has been shown to modulate synaptic plasticity and learning processes in hippocampal excitatory neurons. We found that genetic deletion of HDAC2 specifically from Pv interneurons reduces inhibitory input in the visual cortex of adult mice and coincides with enhanced long-term depression that is more typical of young mice. These findings show that HDAC2 loss in Pv interneurons leads to a delayed closure of the critical period in the visual cortex and supports the hypothesis that HDAC2 is a key negative regulator of synaptic plasticity in the adult brain.
{"title":"HDAC2 expression in parvalbumin interneurons regulates synaptic plasticity in the mouse visual cortex","authors":"Alexi Nott , Sukhee Cho , Jinsoo Seo, Li-Huei Tsai","doi":"10.1016/j.nepig.2014.10.005","DOIUrl":"10.1016/j.nepig.2014.10.005","url":null,"abstract":"<div><p>An experience-dependent postnatal increase in GABAergic inhibition in the visual cortex is important for the closure of a critical period of enhanced synaptic plasticity. Although maturation of the subclass of parvalbumin (Pv)–expressing GABAergic interneurons is known to contribute to critical period closure, the role of epigenetics on cortical inhibition and synaptic plasticity has not been explored. The transcription regulator, histone deacetylase 2 (HDAC2), has been shown to modulate synaptic plasticity and learning processes in hippocampal excitatory neurons. We found that genetic deletion of HDAC2 specifically from Pv interneurons reduces inhibitory input in the visual cortex of adult mice and coincides with enhanced long-term depression that is more typical of young mice. These findings show that HDAC2 loss in Pv interneurons leads to a delayed closure of the critical period in the visual cortex and supports the hypothesis that HDAC2 is a key negative regulator of synaptic plasticity in the adult brain.</p></div>","PeriodicalId":90931,"journal":{"name":"Neuroepigenetics","volume":"1 ","pages":"Pages 34-40"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nepig.2014.10.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33388072","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号