Correction: DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines

ABSTRACTRepeated adaptive divergence in replicates of phenotypic diversification offers a propitious context to identify the molecular bases associated to adaptive divergence. A currently hotly debated topic pertains to the relative role of genomic vs. epigenomic variation in shaping patterns of phenotypic variation at the gene expression level. Here, we combined genomic, epigenomic and transcriptomic information from 64 individuals in order to quantify the relative role of SNPs and DNA methylation variation in the repeated evolution of four limnetic-benthic whitefish species pairs from Europe and North America. We first found evidence for 149 convergent differentially methylated regions (DMRs) between species across continents, which significantly influenced levels of gene expression. Hyper-methylated DMRs in the limnetic species were globally associated to an expression repression relatively to benthic species, and inversely. Furthermore, we identified 108 convergent genetic variants (eQTLs) associated to gene expression differences between species. Gene expression differences were more pronounced in genes harbouring eQTL compared to those associated with DMRs, thus revealing a greater effect of eQTLs on gene expression. Multivariate analyses allowed partitioning the relative contribution of epi-/genomic changes and their association to gene expression variation. Most of the gene expression variation was significantly explained by genomic (4.1%) and putatively genomic-epigenomic interactive variation (46.7%), while “pure” epigenomic variation explained marginally 2.3% of the gene expression variation across continents. This study provides a rare qualitative and quantitative documentation of the relative role of genomic, DNA methylation and their interaction in shaping patterns of convergent gene expression during the process of ecological speciation.

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Faculty Opinions recommendation of Abundant contribution of short tandem repeats to gene expression variation in humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725994101.793513449 ◽

2016 ◽

Author(s):

Melanie Bahlo

Keyword(s):

Gene Expression ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

Gene Expression Variation ◽

Expression Variation ◽

Short Tandem

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DNA Methylation Inhibites ANXA1 Gene Expression in Nasopharyngeal Carcinoma Cell Lines*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2009.00170 ◽

2009 ◽

Vol 36 (10) ◽

pp. 1319-1326 ◽

Cited By ~ 3

Author(s):

Shuang-Xiang TAN ◽

Rui-Cheng HU ◽

Ai-Guo DAI ◽

Cen-E TANG ◽

Hong YI ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Nasopharyngeal Carcinoma Cell ◽

Carcinoma Cell Lines

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Massively parallel gene expression variation measurement of a synonymous codon library

BMC Genomics ◽

10.1186/s12864-021-07462-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alexander Schmitz ◽

Fuzhong Zhang

Keyword(s):

Gene Expression ◽

Codon Usage ◽

Single Cells ◽

Massively Parallel ◽

Protein Abundance ◽

Translation Efficiency ◽

Gene Expression Variation ◽

Expression Variation ◽

Change In Mean ◽

Adaptation Index

Abstract Background Cell-to-cell variation in gene expression strongly affects population behavior and is key to multiple biological processes. While codon usage is known to affect ensemble gene expression, how codon usage influences variation in gene expression between single cells is not well understood. Results Here, we used a Sort-seq based massively parallel strategy to quantify gene expression variation from a green fluorescent protein (GFP) library containing synonymous codons in Escherichia coli. We found that sequences containing codons with higher tRNA Adaptation Index (TAI) scores, and higher codon adaptation index (CAI) scores, have higher GFP variance. This trend is not observed for codons with high Normalized Translation Efficiency Index (nTE) scores nor from the free energy of folding of the mRNA secondary structure. GFP noise, or squared coefficient of variance (CV2), scales with mean protein abundance for low-abundant proteins but does not change at high mean protein abundance. Conclusions Our results suggest that the main source of noise for high-abundance proteins is likely not originating at translation elongation. Additionally, the drastic change in mean protein abundance with small changes in protein noise seen from our library implies that codon optimization can be performed without concerning gene expression noise for biotechnology applications.

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Population transcriptomics uncovers the regulation of gene expression variation in adaptation to changing environment

Scientific Reports ◽

10.1038/srep25536 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 21

Author(s):

Qin Xu ◽

Caiyun Zhu ◽

Yangyang Fan ◽

Zhihong Song ◽

Shilai Xing ◽

...

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

Gene Expression Variation ◽

Changing Environment ◽

Expression Variation

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Gene expression variation increase in trisomy 21 tissues

Mammalian Genome ◽

10.1007/s00335-008-9121-1 ◽

2008 ◽

Vol 19 (6) ◽

pp. 398-405 ◽

Cited By ~ 26

Author(s):

Ching Yu Chou ◽

Li Yu Liu ◽

Chien Yu Chen ◽

Cheng Hsien Tsai ◽

Hsiao Lin Hwa ◽

...

Keyword(s):

Gene Expression ◽

Trisomy 21 ◽

Gene Expression Variation ◽

Expression Variation

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Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.40 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Jessilyn Dunn ◽

Haiwei Qiu ◽

Soyeon Kim ◽

Daudi Jjingo ◽

Ryan Hoffman ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

Methylation Status ◽

Western Diet ◽

Dependent Manner ◽

Gene Promoters ◽

Genome Wide ◽

Methylation Patterns ◽

Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

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