Mouse B2 SINE elements function as IFN-inducible enhancers

Horton, Isabella; Kelly, Conor J; Dziulko, Adam; Simpson, David; Chuong, Edward B.

doi:10.7554/elife.82617

Cited by 13 publications

(5 citation statements)

References 103 publications

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“…Transposable elements (TEs) are genetic "parasites" that constitute over 50% of the human genome 9 . Recently, we and others have shown that TEs are a source of cis-regulatory elements that control immune-inducible expression of immune genes, supporting a role for non-coding TEs in immune regulatory evolution [10][11][12][13][14][15][16] . Here, we investigated the impact of TE-derived exons on the protein-coding transcriptome, focusing on immune genes.…”

Section: Introductionmentioning

confidence: 65%

Regulation of human interferon signaling by transposon exonization

Pasquesi,

Allen,

Ivancevic

et al. 2023

Preprint

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Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues, and functions as a decoy receptor that potently inhibits interferon signaling including in cells infected with SARS-CoV-2. Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.

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Section: Introductionmentioning

confidence: 65%

Regulation of human interferon signaling by transposon exonization

Pasquesi,

Allen,

Ivancevic

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…We speculate that ATRX binding might regulate gene expression changes through a distal enhancer mechanism in the case of ATRX binding sites that do not influence expression of nearby genes. In support of this, ATRX signal was decreased at several types of SINEs in Atrx KO MPCs, including Alu , B2 , B4 , ID and MIR, which act as transcription factor binding sites ( Alu ( 95 ), MIR ( 96 )) or harbor promoter-like ( B2 ) ( 97 ) or enhancer-like features ( B4) ( 98 ), respectively.…”

Section: Discussionmentioning

confidence: 63%

ATRX guards against aberrant differentiation in mesenchymal progenitor cells

Fang,

Barrows,

Dabas

et al. 2024

Nucleic Acids Research

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Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks. We additionally observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Finally, we demonstrated that loss of ATRX in a mesenchymal malignancy, undifferentiated pleomorphic sarcoma, results in similar epigenetic disruption and de-repression of transposable elements. Together, our results reveal a role for ATRX in maintaining epigenetic states and transcriptional repression in mesenchymal progenitors and tumor cells and in preventing aberrant differentiation in the progenitor context.

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“…To evaluate the performance of TEENA, we compared it with BEDtools fisher ( 32 ) and GIGGLE ( 33 ), which has been frequently adopted for TE analysis ( 9 , 14 , 15 , 27 , 36 , 46 ). Of note, a wrapper (i.e.…”

Section: Resultsmentioning

confidence: 99%

TEENA: an integrated web server for transposable element enrichment analysis in various model and non-model organisms

Li,

Lyu,

Chen

et al. 2024

Nucleic Acids Research

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Transposable elements (TEs) are abundant in the genomes of various eukaryote organisms. Increasing evidence suggests that TEs can play crucial regulatory roles—usually by creating cis-elements (e.g. enhancers and promoters) bound by distinct transcription factors (TFs). TE-derived cis-elements have gained unprecedented attentions recently, and one key step toward their understanding is to identify the enriched TEs in distinct genomic intervals (e.g. a set of enhancers or TF binding sites) as candidates for further study. Nevertheless, such analysis remains challenging for researchers unfamiliar with TEs or lack strong bioinformatic skills. Here, we present TEENA (Transposable Element ENrichment Analyzer) to streamline TE enrichment analysis in various organisms. It implements an optimized pipeline, hosts the genome/gene/TE annotations of almost one hundred species, and provides multiple parameters to enable its flexibility. Taking genomic interval data as the only user-supplied file, it can automatically retrieve the corresponding annotations and finish a routine analysis in a couple minutes. Multiple case studies demonstrate that it can produce highly reliable results matching previous knowledge. TEENA can be freely accessed at: https://sun-lab.yzu.edu.cn/TEENA. Due to its easy-to-use design, we expect it to facilitate the studies of the regulatory function of TEs in various model and non-model organisms.

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Mouse B2 SINE elements function as IFN-inducible enhancers

Cited by 13 publications

References 103 publications

Regulation of human interferon signaling by transposon exonization

Regulation of human interferon signaling by transposon exonization

ATRX guards against aberrant differentiation in mesenchymal progenitor cells

TEENA: an integrated web server for transposable element enrichment analysis in various model and non-model organisms

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