DNA Methylation Signatures within the Human Brain
Christine Ladd-Acosta,Jonathan Pevsner,Sarven Sabunciyan,Robert H. Yolken,Maree J. Webster,Tiffany Dinkins,Pauline A. Callinan,Jian Bing Fan,James B. Potash,Andrew P. Feinberg +9 more
TLDR
It is suggested that DNA methylation signatures distinguish brain regions and may help account for region-specific functional specialization in neurological disorders such as Rett syndrome.Abstract:
DNA methylation is a heritable modification of genomic DNA central to development, imprinting, transcriptional regulation, chromatin structure, and overall genomic stability. Aberrant DNA methylation of individual genes is a hallmark of cancer and has been shown to play an important role in neurological disorders such as Rett syndrome. Here, we asked whether normal DNA methylation might distinguish individual brain regions. We determined the quantitative DNA methylation levels of 1,505 CpG sites representing 807 genes with diverse functions, including proliferation and differentiation, previously shown to be implicated in human cancer. We initially analyzed 76 brain samples representing cerebral cortex ( n =35), cerebellum ( n =34), and pons ( n =7), along with liver samples ( n =3) from 43 individuals. Unsupervised hierarchical analysis showed clustering of 33 of 35 cerebra distinct from the clustering of 33 of 34 cerebella, 7 of 7 pons, and all 3 livers. By use of comparative marker selection and permutation testing, 156 loci representing 118 genes showed statistically significant differences—a ⩾17% absolute change in DNA methylation ( Pread more
Citations
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DNA methylation landscapes: provocative insights from epigenomics
Miho Suzuki,Adrian Bird +1 more
TL;DR: The conventional view that DNA methylation functions predominantly to irreversibly silence transcription is being challenged and not only is promoter methylation often highly dynamic during development, but many organisms also seem to targetDNA methylation specifically to the bodies of active genes.
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DNA Methylation and Its Basic Function
Lisa D Moore,Thuc Le,Guoping Fan +2 more
TL;DR: The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders.
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Principles and challenges of genome-wide DNA methylation analysis
TL;DR: There is such a diversity of DNA methylation profiling techniques that it can be challenging to select one, and this Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
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CpG islands--'a rough guide'.
TL;DR: This work has shown that tissue‐specific methylated CGIs localise to regions distal to promoters, the regulatory function of which remains to be determined.
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Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain
J. Raphael Gibbs,J. Raphael Gibbs,Marcel P. van der Brug,Marcel P. van der Brug,Dena G. Hernandez,Dena G. Hernandez,Bryan J. Traynor,Mike A. Nalls,Shiao Lin Lai,Shiao Lin Lai,Sampath Arepalli,Allissa Dillman,Ian Rafferty,Juan C. Troncoso,Robert Johnson,H. Ronald Zielke,Luigi Ferrucci,Dan L. Longo,Mark R. Cookson,Andrew B. Singleton +19 more
TL;DR: A set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome.
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Aharon Razin,Arthur D. Riggs +1 more
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