Gene Expression: Layers of Gene Regulation

Gene Expression: Layers of Gene Regulation

RESEARCH HIGHLIGHTS GENE EXPRESSION methylation. Spearman’s rank cor- relation between methylation levels Layers of gene regulation (within 50 kb on either side of the transcription start site) and alterna- A new study investigates genetic and expression and DNA methylation lev- tive splicing levels show that, for epigenetic influences on genome els often overlap functional elements. many of the genes tested, there is a regulation and alternative splicing, Across cell types, expression quantita- significant association. Of note, many and highlights the tissue specificity of tive trait loci (eQTLs) are enriched in of the associations between DNA some of these interactions. DNase I-hypersensitive sites, whereas methylation and alternative splicing In a previous study, the researchers methylation QTLs (mQTLs) are are cell type-specific, illustrating examined the relationship between enriched in enhancers and insulators. another layer of cellular variability. genetic variation, DNA methyation Their statistical analyses show that, A complex relationship between and gene expression using samples generally, genetic variation has a more DNA methylation and gene expres- from the GenCord cohort that were consistent effect on gene expres- sion is beginning to emerge. This derived from umbilical cords of 204 sion across cell types, although the study further defines the roles of newborn children. They genotyped strength of the effect can be variable. genomic and epigenomic variation 2.5 million single-nucleotide poly- However, the effects of epigenetic in determining cellular phenotypes, morphisms (SNPs), assayed the meth- variation on gene expression are more and the mechanisms by which these ylation levels of 482,421 CpG sites tissue-specific. Methylation sites effects might occur. It also highlights and sequenced the transcriptomes that are associated with expression that regulatory principles and mecha- from three cell types — fibroblasts, levels are found predominantly in nisms identified in one tissue type lymphoblastoid cell lines (LCLs) and enhancers, gene bodies and CpG cannot necessarily be extrapolated to T cells. Extending this work, the team shores, and the correlation with gene other tissue types. now further characterize the effects of expression can be either positive or Bryony Jones genetic and epigenetic variation on the negative. ORIGINAL RESEARCH PAPER tissue specificity of gene expression Alternative splicing levels were Gutierrez-Arcelus, M. et al. Tissue-specific effects and alternative splicing. measured to see whether there of genetic and epigenetic variation on gene regulation and splicing. PLoS Genet. 11, e1004958 Gutierrez-Arcelus et al. find was a tissue-specific correlation (2015) Getty that genetic variation affecting gene with genetic variation and DNA A complex relationship between DNA methylation and gene expression is beginning to emerge NATURE REVIEWS | GENETICS VOLUME 16 | MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved.

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