Transposable elements teach T cells new tricks

Ivancevic, Atma M.; Chuong, Edward B.

doi:10.1073/pnas.2004493117

Cited by 17 publications

(18 citation statements)

References 22 publications

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“…Given the hypothesis that recently active retrotransposons may have facilitated the rapid adaptive evolution undergone by protein-coding immune genes (Chuong et al 2016;Tie et al 2018;Ivancevic and Chuong 2020;Ye et al 2020), it is noteworthy that we find tsVM-IAPs with variable methylation in an immune cell population. We also found an inverse correlation between the methylation level of a tsVM-IAP and gene expression; the transcriptional effect was specific to B cells, despite the presence of variable methylation in other tissue types.…”

Section: Discussionmentioning

confidence: 78%

Genomic properties of variably methylated retrotransposons in mouse

Elmer

Hay

Kessler

et al. 2020

Preprint

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Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.

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Section: Discussionmentioning

confidence: 78%

Genomic properties of variably methylated retrotransposons in mouse

Elmer

Hay

Kessler

et al. 2020

Preprint

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“…The genome-wide contribution of TEs to gene regulation has been studied in several relevant phenotypes such as development, response to xenobiotics, immune response, and disease [23,[27][28][29]. While there are several studies highlighting the potential role of TE insertions in the regulation of the immune response [30][31][32], whether TEs are more often recruited to play a role in immune response remains speculative [33].…”

Section: Introductionmentioning

confidence: 99%

Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

2021

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Background Variation in gene expression underlies interindividual variability in relevant traits including immune response. However, the genetic variation responsible for these gene expression changes remains largely unknown. Among the non-coding variants that could be relevant, transposable element insertions are promising candidates as they have been shown to be a rich and diverse source of cis-regulatory elements. Results In this work, we use a population genetics approach to identify transposable element insertions likely to increase the tolerance of Drosophila melanogaster to bacterial infection by affecting the expression of immune-related genes. We identify 12 insertions associated with allele-specific expression changes in immune-related genes. We experimentally validate three of these insertions including one likely to be acting as a silencer, one as an enhancer, and one with a dual role as enhancer and promoter. The direction in the change of gene expression associated with the presence of several of these insertions is consistent with an increased survival to infection. Indeed, for one of the insertions, we show that this is the case by analyzing both natural populations and CRISPR/Cas9 mutants in which the insertion is deleted from its native genomic context. Conclusions We show that transposable elements contribute to gene expression variation in response to infection in D. melanogaster and that this variation is likely to affect their survival capacity. Because the role of transposable elements as regulatory elements is not restricted to Drosophila, transposable elements are likely to play a role in immune response in other organisms as well.

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“…The genome-wide contribution of TEs to gene regulation has been studied in several relevant phenotypes such as development, response to xenobiotics, immune response, and disease (23, 27–29). While there are several studies highlighting the potential role of TE insertions in the regulation of the immune response (30–32), whether TEs are more often recruited to play a role in immune response remains speculative (33).…”

Section: Introductionmentioning

confidence: 99%

Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

Ullastres

Merenciano

González

2019

Preprint

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Variation in gene expression underlies inter-individual variability in immune response.However, the mutations responsible for gene expression changes remain largely unknown. In this work, we searched for transposable element insertions present at high population frequencies and located nearby immune-related genes in Drosophila melanogaster. We identified 12 insertions associated with allele-specific expression changes in immune-related genes. We showed that transgenically induced expression changes in most of these genes are associated with differences in survival to infection with the gram-negative bacteria Pseudomonas entomophila. We provide experimental evidence suggesting a causal role for five insertions in the allele-specific expression changes observed. Furthermore, for two insertions we found a significant association with increased tolerance to bacterial infection. Our results showed for the first time that polymorphic transposable element insertions from different families drive expression changes in genes that are relevant for inter-individual differences in immune response.

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Transposable elements teach T cells new tricks

Cited by 17 publications

References 22 publications

Genomic properties of variably methylated retrotransposons in mouse

Genomic properties of variably methylated retrotransposons in mouse

Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila

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