scholarly journals Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Lucas T. Husquin ◽  
Maxime Rotival ◽  
Maud Fagny ◽  
Hélène Quach ◽  
Nora Zidane ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Human Population ◽  
Genetic Basis ◽  
Immune Gene ◽  
Population Differences ◽  
Causal Impact

scholarly journals Exploring the Genetic Basis of Human Population Differences in DNA Methylation and their Causal Impact on Immune Gene Regulation

2018 ◽  
Author(s):  
Lucas T. Husquin ◽  
Maxime Rotival ◽  
Maud Fagny ◽  
Hélène Quach ◽  
Nora Zidane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Complex Traits ◽  
Active Role ◽  
System Level ◽  
Immune Gene ◽  
Population Differences ◽  
Mediation Effects ◽  
Causal Impact

AbstractDNA methylation is influenced by both environmental and genetic factors and is increasingly thought to affect variation in complex traits and diseases. Yet, the extent of ancestry-related differences in DNA methylation, its genetic determinants, and their respective causal impact on immune gene regulation remain elusive. We report extensive population differences in DNA methylation between individuals of African and European descent — detected in primary monocytes that were used as a model of a major innate immunity cell type. Most of these differences (~70%) were driven by DNA sequence variants nearby CpG sites (meQTLs), which account for ~60% of the variance in DNA methylation. We also identify several master regulators of DNA methylation variation in trans, including a regulatory hub nearby the transcription factor-encoding CTCF gene, which contributes markedly to ancestry-related differences in DNA methylation. Furthermore, we establish that variation in DNA methylation is associated with varying gene expression levels following mostly, but not exclusively, a canonical model of negative associations, particularly in enhancer regions. Specifically, we find that DNA methylation highly correlates with transcriptional activity of 811 and 230 genes, at the basal state and upon immune stimulation, respectively. Finally, using a Bayesian approach, we estimate causal mediation effects of DNA methylation on gene expression in ~20% of the studied cases, indicating that DNA methylation can play an active role in immune gene regulation. Using a system-level approach, our study reveals substantial ancestry-related differences in DNA methylation and provides evidence for their causal impact on immune gene regulation.

scholarly journals Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Carmeli ◽  
Zoltán Kutalik ◽  
Pashupati P. Mishra ◽  
Eleonora Porcu ◽  
Cyrille Delpierre ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Cohort Studies ◽  
Early Life ◽  
Life Experiences ◽  
Socioeconomic Disadvantage ◽  
Mediating Role ◽  
The Impact ◽  
The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

Environmental Exposure, DNA Methylation, and Gene Regulation

2003 ◽  
Vol 983 (1) ◽  
pp. 161-169 ◽  
Author(s):  
SHUANFANG LI ◽  
STEPHEN D. HURSTING ◽  
BARBARA J. DAVIS ◽  
JOHN A. McLACHLAN ◽  
J. CARL BARRETT
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Environmental Exposure

scholarly journals Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation

Biology Open ◽  
2016 ◽  
Vol 5 (8) ◽  
pp. 1134-1141 ◽  
Author(s):  
Ellen I. Hartig ◽  
Shusen Zhu ◽  
Benjamin L. King ◽  
James A. Coffman
Keyword(s):  
Gene Regulation ◽  
Zebrafish Embryos ◽  
Immune Gene

scholarly journals Intra- and Inter-Specific Investigations of Skeletal DNA Methylation and Femur Morphology in Primates

2019 ◽  
Author(s):  
Genevieve Housman ◽  
Ellen E. Quillen ◽  
Anne C. Stone
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Biological Effects ◽  
Epigenetic Mechanism ◽  
Primate Species ◽  
Phylogenetic Groups ◽  
Skeletal Morphology ◽  
Specific Variation ◽  
Morphological Variants ◽  
Species Specific

AbstractObjectivesEpigenetic mechanisms influence the development and maintenance of complex phenotypes and may also contribute to the evolution of species-specific phenotypes. With respect to skeletal traits, little is known about the gene regulation underlying these hard tissues or how tissue-specific patterns are associated with bone morphology or vary among species. To begin exploring these topics, this study evaluates one epigenetic mechanism, DNA methylation, in skeletal tissues from five nonhuman primate species which display anatomical and locomotor differences representative of their phylogenetic groups.Materials and MethodsFirst, we test whether intra-specific variation in skeletal DNA methylation is associated with intra-specific variation in femur morphology. Second, we identify inter-specific differences in DNA methylation and assess whether these lineage-specific patterns may have contributed to species-specific morphologies. Specifically, we use the Illumina Infinium MethylationEPIC BeadChip to identify DNA methylation patterns in femur trabecular bone from baboons (n=28), macaques (n=10), vervets (n=10), chimpanzees (n=4), and marmosets (n=6).ResultsSignificant differentially methylated positions (DMPs) were associated with a subset of morphological variants, but these likely have small biological effects and may be confounded by other variables associated with morphological variation. Conversely, several species-specific DMPs were identified, and these are found in genes enriched for functions associated with complex skeletal traits.DiscussionOverall, these findings reveal that while intra-specific epigenetic variation is not readily associated with skeletal morphology differences, some inter-specific epigenetic differences in skeletal tissues exist and may contribute to evolutionarily distinct phenotypes. This work forms a foundation for future explorations of gene regulation and skeletal trait evolution in primates.

scholarly journals Correction: Passive and active DNA methylation and the interplay with genetic variation in gene regulation

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Maria Gutierrez-Arcelus ◽  
Tuuli Lappalainen ◽  
Stephen B Montgomery ◽  
Alfonso Buil ◽  
Halit Ongen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Genetic Variation

scholarly journals Invertebrate DNA Methylation and Gene Regulation

2021 ◽  
Author(s):  
Groves Dixon ◽  
Mikhail Matz
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Environmental Change ◽  
Linear Relationship ◽  
Differential Expression ◽  
Differential Methylation ◽  
Simple Relationship ◽  
Simple Linear Relationship

Abstract BackgroundAs human activity alters the planet, there is a pressing need to understand how organisms adapt to environmental change. Of growing interest in this area is the role of epigenetic modifications, such as DNA methylation, in tailoring gene expression to fit novel conditions. Here, we reanalyzed nine invertebrate (Anthozoa and Hexapoda) datasets to validate a key prediction of this hypothesis: changes in DNA methylation in response to some condition correlate with changes in gene expression. ResultsWhile we detected both differential methylation and differential expression, there was no simple relationship between these differences. ConclusionIf changes in DNA methylation regulate invertebrate transcription, the mechanism does not follow a simple linear relationship.

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