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| Open AccessDiurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer’s disease
Diurnal and seasonal rhythms modulate brain function, but we do not know the genomic basis for these rhythms. Here, Limet al. show diurnal and seasonal rhythms of gene expression in the human brain, their relationship to histone acetylation and DNA methylation, and their disruption in Alzheimer’s disease.
- Andrew S. P. Lim
- , Hans-Ulrich Klein
- & Philip L. De Jager
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Article
| Open AccessDNA methylation signatures in peripheral blood strongly predict all-cause mortality
DNA methylation is modulated by environmental factors and has a role in many complex diseases. Here, the authors find that methylation at specific DNA sites is associated with all-cause mortality, and a methylation-based risk score may be informative for risk assessment and stratification.
- Yan Zhang
- , Rory Wilson
- & Hermann Brenner
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Article
| Open AccessThe SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers
SWI/SNF chromatin remodelling complex is a major regulator of chromatin structure and of transcription. Here, using mouse embryonic fibroblasts and human rhabdoid tumour cells, the authors provide evidence that SWI/SNF functions as a regulator of enhancers.
- Burak H. Alver
- , Kimberly H. Kim
- & Charles W. M. Roberts
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| Open AccessHotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome
Active enhancers are defined by the presence of post-translational modifications of histones. Here, the authors use these marks to identify enhancers recurrently activated in colorectal cancer and find that these enhancers turn on oncogenes and are associated with known risk loci for developing the disease.
- Andrea J. Cohen
- , Alina Saiakhova
- & Peter C. Scacheri
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Article
| Open AccessIncreased DNA methylation variability in type 1 diabetes across three immune effector cell types
The incidence of type 1 diabetes is increasing, potentially implicating non-genetic factors. Here the authors conduct an epigenome-wide association study in disease-discordant twins and find increased DNA methylation variability at genes associated with immune cell metabolism and the cell cycle.
- Dirk S. Paul
- , Andrew E. Teschendorff
- & R. David Leslie
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| Open Access5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients
Glioblastomas have distorted epigenomes. Here, the authors compare the genome-wide profiles of 5-methylcytosine and 5- hydroxymethylcytosine in glioblastoma and prefrontal cortex tissue reporting a correlation between these profiles and patients’ prognosis.
- Kevin C. Johnson
- , E. Andres Houseman
- & Brock C. Christensen
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Article
| Open AccessGenome-wide compendium and functional assessment of in vivo heart enhancers
Identification of non-coding variants has outstripped our ability to annotate and interpret them. Dickel et al. present a compendium of over 80,000 putative human heart enhancers and demonstrate that two conserved enhancers are required for proper cardiac function in mice.
- Diane E. Dickel
- , Iros Barozzi
- & Len A. Pennacchio
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| Open AccessCapture of associated targets on chromatin links long-distance chromatin looping to transcriptional coordination
Chromatin architecture is a key regulator of transcriptional processes, however current methods to investigate it have technical limitations. Here, the authors describe a novel chromatin capture technique, CATCH, which can be used to identify and characterize complex genomic interaction networks.
- Ryan J. Bourgo
- , Hari Singhal
- & Geoffrey L. Greene
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Article
| Open AccessLongitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex
Chromosome conformation is a dynamic process, especially in brain. Here, Mitchell and colleagues devise a method they call NeuroDam that can prospectively tag chromosome conformation in the mouse brain in vivo, and longitudinally assess long range chromosome looping weeks and months later.
- Amanda C. Mitchell
- , Behnam Javidfar
- & Schahram Akbarian
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| Open AccessChromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks
Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity. Here, the authors report the genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using ATAC-seq, and 10 matched RNA-seq datasets, providing a resource for studying epigenome deregulation in CLL.
- André F. Rendeiro
- , Christian Schmidl
- & Christoph Bock
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Article
| Open AccessGenetic and environmental influences interact with age and sex in shaping the human methylome
Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation.
- Jenny van Dongen
- , Michel G. Nivard
- & Dorret I. Boomsma
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| Open AccessConstructing 3D interaction maps from 1D epigenomes
The human genome is highly organized, with one-dimensional chromatin states packaged into higher level three-dimensional architecture. Here, the authors present EpiTensor that can identify 3D spatial associations from 1D epigenetic information.
- Yun Zhu
- , Zhao Chen
- & Wei Wang
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| Open AccessThe epigenomic landscape of African rainforest hunter-gatherers and farmers
Genetic and environmental factors affect genome-wide patterns of epigenetic variation. Here, the authors show that while current habitat and historical lifestyle impact the methylome of rainforest hunter-gatherers and sedentary farmers, the biological functions affected and the degree of genetic control differ.
- Maud Fagny
- , Etienne Patin
- & Lluis Quintana-Murci
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High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq
Characterizing mammalian gene expression regulation by enhancer elements is complicated by the size and complexity of the genome. Here Vanhille et al.demonstrate CapStarr-Seq, a novel high-throughput method for assessing potential enhancers and deciphering the mechanisms regulating transcription
- Laurent Vanhille
- , Aurélien Griffon
- & Salvatore Spicuglia
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| Open AccessArabidopsis MSH1 mutation alters the epigenome and produces heritable changes in plant growth
Suppression of MutS HOMOLOGUE 1 (MSH1), a plant protein targeted to mitochondria and plastids, causes a variety of phenotypes. Here Virdi et al. show that MSH1 depletion in Arabidopsisresults in heritable changes in nuclear DNA methylation, which can lead to enhanced growth vigour.
- Kamaldeep S. Virdi
- , John D. Laurie
- & Sally A. Mackenzie
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| Open AccessEpigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs
Tissue-specific functions have been established for some lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, the authors report tissue-specific epigenomic regulation of 3,753 lincRNAs and their strong connection with tissue-specific pathways.
- Viren Amin
- , R. Alan Harris
- & Aleksandar Milosavljevic
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Article
| Open AccessEpigenetic and transcriptional determinants of the human breast
Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.
- Philippe Gascard
- , Misha Bilenky
- & Martin Hirst
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Regulatory network decoded from epigenomes of surface ectoderm-derived cell types
Epigenomes are thought to retain molecular memories of their developmental history. Here, by comparing differentially methylated regions of genomes from different cells, the authors reveal an epigenetic signature that underlies a shared gene regulatory network with a common developmental origin.
- Rebecca F. Lowdon
- , Bo Zhang
- & Jeffrey B. Cheng
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The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences
There is epigenetic variability in the same cell type among healthy individuals, but the mechanism or significance of this variability is not clear. Here, the authors purify CD34+ cells from different individuals and use meta-epigenomic approaches to analyse and explain the epigenetic variability observed.
- N. Ari Wijetunga
- , Fabien Delahaye
- & John M. Greally
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| Open AccessAncestral repeats have shaped epigenome and genome composition for millions of years in Arabidopsis thaliana
Repeated sequences are common in genomes, yet little is known about the long-term evolution of repeats in plants. Here, Maumus and Quesneville show that most of the repeated sequences in the model plant, Arabidopsis thaliana, are old and that many small RNAs correspond to old repeats.
- Florian Maumus
- & Hadi Quesneville
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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.
- Mark Wossidlo
- , Toshinobu Nakamura
- & Jörn Walter