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The epigenetic consequences of chronic HIV infection
Individuals infected with HIV are live for many decades, thanks to the advances made to anti-retroviral drugs. However, chronic HIV infection has been linked to early-onset neurodegeneration, cancer and telomere shortening – potential signs of premature aging.
Aging is associated with epigenetic changes, and previous research has used CpG DNA methylation patterns to predict the age of individuals. To test the hypothesis that HIV-positive patients experience advanced or accelerated aging, a team led by Trey Ideker from the University of California, San Diego performed a global DNA methylation analysis of HIV-positive individuals. They found the following:
The results presented in this paper show that HIV infection results in epigenetic changes that mirror age-related DNA methylation and influence regulation of HLA.
Read the full paper in Molecular Cell, April 2016.
DNA methylation variation is affected by genetic and environmental factors
DNA methylation contributes to long-term gene expression regulation. Changes to DNA methylation occur in response to environmental and genetic stimuli, but these factors may affect the methylome differently depending on age and sex.
To estimate between-individual variation in DNA methylation, a team led by Dorret Boomsma from Vrije Universiteit in Amsterdam analyzed DNA methylation data from a large cohort of twins and family members. They found the following:
This is the most comprehensive study to date to look at the importance of genetic and environmental factors on DNA methylation variation. The authors have cataloged genetic and environmental influences on DNA methylation across the genome.
Read the full paper in Nature Communications, April 2016.
A new technique to study post-replication chromatin assembly
DNA replication involves disruption of the nucleosomes to allow DNA replication machinery to pass. Chromatin state is re-established by chromatin regulators; however, the sequence of events that re-establishes chromatin state after the replication fork passes is not known. Research on this topic has been limited by current methods to map newly replicated DNA, which provide data at kilobase resolution.
To map the newly replicated epigenome at base-pair resolution, a team led by Steven Henikoff from the Fred Hutchinson Cancer Research Center and Howard Hughes Medical Institute in Seattle developed a technique called mapping in vivo nascent chromatin with EdU and sequencing (MINCE-seq).
In this technique, newly replicated DNA is labeled with EdU, which is coupled with biotin for highly specific purification of newly replicated DNA. DNA fragments, nucleosomes and DNA-binding proteins are recovered, and chromatin mapped. Using this technique, the team were able to characterize the chromosome landscape in Drosophila melanogaster cells:
The authors have shown that MINCE-seq is capable of mapping newly replicated chromatin. Using this technique, they were able to identify changes in chromatin post replication.
Read the full paper in Cell, April 2016.
A complex picture of enhancer histone acetylation
Acetylation and methylation of globular histone domains can alter chromatin structure, and assembly, and affect genome stability. However, many previous studies have focused on aceylation of histone tails rather than globular domains.
To gain a better understanding of histone acetylation, a team led by Wendy Bickmore from the University of Edinburgh looked at histone acetylation in the globular domain of histone H3. Here is what they found:
This paper paints a complex picture of histone acetylation at enhancers. The authors have demonstrated that identification of enhancers requires a more comprehensive analysis of histone acetylation than previously thought.
Read the full paper in Nature Genetics, April 2016.
α-synuclein is regulated by a non-coding distal enhancer
The vast majority of Parkinson's disease cases result from complex interactions between genetic and environmental risk factors. Mutations and duplications in the α-synuclein (SNCA) gene has been implicated in both familial and sporadic cases of Parkinson's disease, with just small increases in gene expression thought to be sufficient to contribute to disease development.
To analyze small changes in SNCA gene expression, a team led by Rudolf Jaenisch at the Whitehead Institute in Cambridge, Massachusetts combined genome-wide epigenetic information with CRISPR/Cas9 genome editing to quantify the consequences of targeted genetic modification. They found the following:
In this paper, the authors have identified a Parkinson's disease risk variant in a non-coding distal enhancer element that regulates expression of α-synuclein.
Read the full paper in Nature, April 2016.
Lnc13 regulates inflammatory genes associated with celiac disease
Celiac disease is a chronic, immune-mediated intestinal disorder that develops in genetically-susceptible individuals. Previously, 14 intergenic SNPs associated with celiac disease were identified. One of these SNPs is in a region that encodes lnc13 in mice.
A team led by Sankar Ghosh from the University of Somewhere sought to characterize the role of lnc13 in celiac disease in humans. They found the following:
The results in the paper suggest that lnc13 down-regulation may contribute to the inflammation seen in celiac disease, and that this protein regulates inflammatory genes by linking hnRNPD, Hdac1 and chromatin.
Read the full paper in Science, April 2016.