Mobile DNAPub Date : 2024-10-09DOI: 10.1186/s13100-024-00330-z
Md Fakhrul Azad, Tong Tong, Nelson C Lau
{"title":"Transposable Element (TE) insertion predictions from RNAseq inputs and TE impact on RNA splicing and gene expression in Drosophila brain transcriptomes.","authors":"Md Fakhrul Azad, Tong Tong, Nelson C Lau","doi":"10.1186/s13100-024-00330-z","DOIUrl":"10.1186/s13100-024-00330-z","url":null,"abstract":"<p><p>Recent studies have suggested that Transposable Elements (TEs) residing in introns frequently splice into and alter primary gene-coding transcripts. To re-examine the exonization frequency of TEs into protein-coding gene transcripts, we re-analyzed a Drosophila neuron circadian rhythm RNAseq dataset and a deep long RNA fly midbrain RNAseq dataset using our Transposon Insertion and Depletion Analyzer (TIDAL) program. Our TIDAL results were able to predict several TE insertions from RNAseq data that were consistent with previous published studies. However, we also uncovered many discrepancies in TE-exonization calls, such as reads that mainly support intron retention of the TE and little support for chimeric mRNA spliced to the TE. We then deployed rigorous genomic DNA-PCR (gDNA-PCR) and RT-PCR procedures on TE-mRNA fusion candidates to see how many of bioinformatics predictions could be validated. By testing a w1118 strain from which the deeper long RNAseq data was derived and comparing to an OreR strain, only 9 of 23 TIDAL candidates (< 40%) could be validated as a novel TE insertion by gDNA-PCR, indicating that deeper study is needed when using RNAseq data as inputs into current TE-insertion prediction programs. Of these validated calls, our RT-PCR results only supported TE-intron retention. Lastly, in the Dscam2 and Bx genes of the w1118 strain that contained intronic TEs, gene expression was 23 times higher than the OreR genes lacking the TEs. This study's validation approach indicates that chimeric TE-mRNAs are infrequent and cautions that more optimization is required in bioinformatics programs to call TE insertions using RNAseq datasets.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"20"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-10-09DOI: 10.1186/s13100-024-00333-w
Erin E Grundy, Lauren C Shaw, Loretta Wang, Abigail V Lee, James Castro Argueta, Daniel J Powell, Mario Ostrowski, R Brad Jones, C Russell Y Cruz, Heather Gordish-Dressman, Nicole P Chappell, Catherine M Bollard, Katherine B Chiappinelli
{"title":"A T cell receptor specific for an HLA-A*03:01-restricted epitope in the endogenous retrovirus ERV-K-Env exhibits limited recognition of its cognate epitope.","authors":"Erin E Grundy, Lauren C Shaw, Loretta Wang, Abigail V Lee, James Castro Argueta, Daniel J Powell, Mario Ostrowski, R Brad Jones, C Russell Y Cruz, Heather Gordish-Dressman, Nicole P Chappell, Catherine M Bollard, Katherine B Chiappinelli","doi":"10.1186/s13100-024-00333-w","DOIUrl":"10.1186/s13100-024-00333-w","url":null,"abstract":"<p><p>Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"19"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-10-01DOI: 10.1186/s13100-024-00328-7
Mohadeseh S Tahami, Carlos Vargas-Chavez, Noora Poikela, Marta Coronado-Zamora, Josefa González, Maaria Kankare
{"title":"Transposable elements in Drosophila montana from harsh cold environments.","authors":"Mohadeseh S Tahami, Carlos Vargas-Chavez, Noora Poikela, Marta Coronado-Zamora, Josefa González, Maaria Kankare","doi":"10.1186/s13100-024-00328-7","DOIUrl":"10.1186/s13100-024-00328-7","url":null,"abstract":"<p><strong>Background: </strong>Substantial discoveries during the past century have revealed that transposable elements (TEs) can play a crucial role in genome evolution by affecting gene expression and inducing genetic rearrangements, among other molecular and structural effects. Yet, our knowledge on the role of TEs in adaptation to extreme climates is still at its infancy. The availability of long-read sequencing has opened up the possibility to identify and study potential functional effects of TEs with higher precision. In this work, we used Drosophila montana as a model for cold-adapted organisms to study the association between TEs and adaptation to harsh climates.</p><p><strong>Results: </strong>Using the PacBio long-read sequencing technique, we de novo identified and manually curated TE sequences in five Drosophila montana genomes from eco-geographically distinct populations. We identified 489 new TE consensus sequences which represented 92% of the total TE consensus in D. montana. Overall, 11-13% of the D. montana genome is occupied by TEs, which as expected are non-randomly distributed across the genome. We identified five potentially active TE families, most of them from the retrotransposon class of TEs. Additionally, we found TEs present in the five analyzed genomes that were located nearby previously identified cold tolerant genes. Some of these TEs contain promoter elements and transcription binding sites. Finally, we detected TEs nearby fixed and polymorphic inversion breakpoints.</p><p><strong>Conclusions: </strong>Our research revealed a significant number of newly identified TE consensus sequences in the genome of D. montana, suggesting that non-model species should be studied to get a comprehensive view of the TE repertoire in Drosophila species and beyond. Genome annotations with the new D. montana library allowed us to identify TEs located nearby cold tolerant genes, and present at high population frequencies, that contain regulatory regions and are thus good candidates to play a role in D. montana cold stress response. Finally, our annotations also allow us to identify for the first time TEs present in the breakpoints of three D. montana inversions.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"18"},"PeriodicalIF":4.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-09-05DOI: 10.1186/s13100-024-00327-8
Ezequiel G Mogro, Walter O Draghi, Antonio Lagares, Mauricio J Lozano
{"title":"Identification and functional analysis of recent IS transposition events in rhizobia.","authors":"Ezequiel G Mogro, Walter O Draghi, Antonio Lagares, Mauricio J Lozano","doi":"10.1186/s13100-024-00327-8","DOIUrl":"10.1186/s13100-024-00327-8","url":null,"abstract":"<p><p>Rhizobia are alpha- and beta- Proteobacteria that, through the establishment of symbiotic interactions with leguminous plants, are able to fix atmospheric nitrogen as ammonium. The successful establishment of a symbiotic interaction is highly dependent on the availability of nitrogen sources in the soil, and on the specific rhizobia strain. Insertion sequences (ISs) are simple transposable genetic elements that can move to different locations within the host genome and are known to play an important evolutionary role, contributing to genome plasticity by acting as recombination hot-spots, and disrupting coding and regulatory sequences. Disruption of coding sequences may have occurred either in a common ancestor of the species or more recently. By means of ISComapare, we identified Differentially Located ISs (DLISs) in nearly related rhizobial strains of the genera Bradyrhizobium, Mesorhizobium, Rhizobium and Sinorhizobium. Our results revealed that recent IS transposition could have a role in adaptation by enabling the activation and inactivation of genes that could dynamically affect the competition and survival of rhizobia in the rhizosphere.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-08-05DOI: 10.1186/s13100-024-00326-9
Matthias Heuberger, Dal-Hoe Koo, Hanin Ibrahim Ahmed, Vijay K Tiwari, Michael Abrouk, Jesse Poland, Simon G Krattinger, Thomas Wicker
{"title":"Evolution of Einkorn wheat centromeres is driven by the mutualistic interplay of two LTR retrotransposons.","authors":"Matthias Heuberger, Dal-Hoe Koo, Hanin Ibrahim Ahmed, Vijay K Tiwari, Michael Abrouk, Jesse Poland, Simon G Krattinger, Thomas Wicker","doi":"10.1186/s13100-024-00326-9","DOIUrl":"10.1186/s13100-024-00326-9","url":null,"abstract":"<p><strong>Background: </strong>Centromere function is highly conserved across eukaryotes, but the underlying centromeric DNA sequences vary dramatically between species. Centromeres often contain a high proportion of repetitive DNA, such as tandem repeats and/or transposable elements (TEs). Einkorn wheat centromeres lack tandem repeat arrays and are instead composed mostly of the two long terminal repeat (LTR) retrotransposon families RLG_Cereba and RLG_Quinta which specifically insert in centromeres. However, it is poorly understood how these two TE families relate to each other and if and how they contribute to centromere function and evolution.</p><p><strong>Results: </strong>Based on conservation of diagnostic motifs (LTRs, integrase and primer binding site and polypurine-tract), we propose that RLG_Cereba and RLG_Quinta are a pair of autonomous and non-autonomous partners, in which the autonomous RLG_Cereba contributes all the proteins required for transposition, while the non-autonomous RLG_Quinta contributes GAG protein. Phylogenetic analysis of predicted GAG proteins showed that the RLG_Cereba lineage was present for at least 100 million years in monocotyledon plants. In contrast, RLG_Quinta evolved from RLG_Cereba between 28 and 35 million years ago in the common ancestor of oat and wheat. Interestingly, the integrase of RLG_Cereba is fused to a so-called CR-domain, which is hypothesized to guide the integrase to the functional centromere. Indeed, ChIP-seq data and TE population analysis show only the youngest subfamilies of RLG_Cereba and RLG_Quinta are found in the active centromeres. Importantly, the LTRs of RLG_Quinta and RLG_Cereba are strongly associated with the presence of the centromere-specific CENH3 histone variant. We hypothesize that the LTRs of RLG_Cereba and RLG_Quinta contribute to wheat centromere integrity by phasing and/or placing CENH3 nucleosomes, thus favoring their persistence in the competitive centromere-niche.</p><p><strong>Conclusion: </strong>Our data show that RLG_Cereba cross-mobilizes the non-autonomous RLG_Quinta retrotransposons. New copies of both families are specifically integrated into functional centromeres presumably through direct binding of the integrase CR domain to CENH3 histone variants. The LTRs of newly inserted RLG_Cereba and RLG_Quinta elements, in turn, recruit and/or phase new CENH3 deposition. This mutualistic interplay between the two TE families and the plant host dynamically maintains wheat centromeres.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"16"},"PeriodicalIF":4.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-07-27DOI: 10.1186/s13100-024-00325-w
Weronika Mikina, Paweł Hałakuc, Rafał Milanowski
{"title":"Transposon-derived introns as an element shaping the structure of eukaryotic genomes","authors":"Weronika Mikina, Paweł Hałakuc, Rafał Milanowski","doi":"10.1186/s13100-024-00325-w","DOIUrl":"https://doi.org/10.1186/s13100-024-00325-w","url":null,"abstract":"The widely accepted hypothesis postulates that the first spliceosomal introns originated from group II self-splicing introns. However, it is evident that not all spliceosomal introns in the nuclear genes of modern eukaryotes are inherited through vertical transfer of intronic sequences. Several phenomena contribute to the formation of new introns but their most common origin seems to be the insertion of transposable elements. Recent analyses have highlighted instances of mass gains of new introns from transposable elements. These events often coincide with an increase or change in the spliceosome's tolerance to splicing signals, including the acceptance of noncanonical borders. Widespread acquisitions of transposon-derived introns occur across diverse evolutionary lineages, indicating convergent processes. These events, though independent, likely require a similar set of conditions. These conditions include the presence of transposon elements with features enabling their removal at the RNA level as introns and/or the existence of a splicing mechanism capable of excising unusual sequences that would otherwise not be recognized as introns by standard splicing machinery. Herein we summarize those mechanisms across different eukaryotic lineages.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"62 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-06-27DOI: 10.1186/s13100-024-00324-x
Fatemeh Moadab, Sepideh Sohrabi, Xiaoxing Wang, Rayan Najjar, Justina C Wolters, Hua Jiang, Wenyan Miao, Donna Romero, Dennis M Zaller, Megan Tran, Alison Bays, Martin S Taylor, Rosana Kapeller, John LaCava, Tomas Mustelin
{"title":"Subcellular location of L1 retrotransposon-encoded ORF1p, reverse transcription products, and DNA sensors in lupus granulocytes.","authors":"Fatemeh Moadab, Sepideh Sohrabi, Xiaoxing Wang, Rayan Najjar, Justina C Wolters, Hua Jiang, Wenyan Miao, Donna Romero, Dennis M Zaller, Megan Tran, Alison Bays, Martin S Taylor, Rosana Kapeller, John LaCava, Tomas Mustelin","doi":"10.1186/s13100-024-00324-x","DOIUrl":"10.1186/s13100-024-00324-x","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unpredictable course of recurrent exacerbations alternating with more stable disease. SLE is characterized by broad immune activation and autoantibodies against double-stranded DNA and numerous proteins that exist in cells as aggregates with nucleic acids, such as Ro60, MOV10, and the L1 retrotransposon-encoded ORF1p.</p><p><strong>Results: </strong>Here we report that these 3 proteins are co-expressed and co-localized in a subset of SLE granulocytes and are concentrated in cytosolic dots that also contain DNA: RNA heteroduplexes and the DNA sensor ZBP1, but not cGAS. The DNA: RNA heteroduplexes vanished from the neutrophils when they were treated with a selective inhibitor of the L1 reverse transcriptase. We also report that ORF1p granules escape neutrophils during the extrusion of neutrophil extracellular traps (NETs) and, to a lesser degree, from neutrophils dying by pyroptosis, but not apoptosis.</p><p><strong>Conclusions: </strong>These results bring new insights into the composition of ORF1p granules in SLE neutrophils and may explain, in part, why proteins in these granules become targeted by autoantibodies in this disease.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"14"},"PeriodicalIF":4.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-06-26DOI: 10.1186/s13100-024-00323-y
Pío Sierra, Richard Durbin
{"title":"Identification of transposable element families from pangenome polymorphisms.","authors":"Pío Sierra, Richard Durbin","doi":"10.1186/s13100-024-00323-y","DOIUrl":"10.1186/s13100-024-00323-y","url":null,"abstract":"<p><strong>Background: </strong>Transposable Elements (TEs) are segments of DNA, typically a few hundred base pairs up to several tens of thousands bases long, that have the ability to generate new copies of themselves in the genome. Most existing methods used to identify TEs in a newly sequenced genome are based on their repetitive character, together with detection based on homology and structural features. As new high quality assemblies become more common, including the availability of multiple independent assemblies from the same species, an alternative strategy for identification of TE families becomes possible in which we focus on the polymorphism at insertion sites caused by TE mobility.</p><p><strong>Results: </strong>We develop the idea of using the structural polymorphisms found in pangenomes to create a library of the TE families recently active in a species, or in a closely related group of species. We present a tool, pantera, that achieves this task, and illustrate its use both on species with well-curated libraries, and on new assemblies.</p><p><strong>Conclusions: </strong>Our results show that pantera is sensitive and accurate, tending to correctly identify complete elements with precise boundaries, and is particularly well suited to detect larger, low copy number TEs that are often undetected with existing de novo methods.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"13"},"PeriodicalIF":4.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11202377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-06-11DOI: 10.1186/s13100-024-00322-z
Chris J Frangieh, Max E Wilkinson, Daniel Strebinger, Jonathan Strecker, Michelle L Walsh, Guilhem Faure, Irina A Yushenova, Rhiannon K Macrae, Irina R Arkhipova, Feng Zhang
{"title":"Internal initiation of reverse transcription in a Penelope-like retrotransposon.","authors":"Chris J Frangieh, Max E Wilkinson, Daniel Strebinger, Jonathan Strecker, Michelle L Walsh, Guilhem Faure, Irina A Yushenova, Rhiannon K Macrae, Irina R Arkhipova, Feng Zhang","doi":"10.1186/s13100-024-00322-z","DOIUrl":"10.1186/s13100-024-00322-z","url":null,"abstract":"<p><p>Eukaryotic retroelements are generally divided into two classes: long terminal repeat (LTR) retrotransposons and non-LTR retrotransposons. A third class of eukaryotic retroelement, the Penelope-like elements (PLEs), has been well-characterized bioinformatically, but relatively little is known about the transposition mechanism of these elements. PLEs share some features with the R2 retrotransposon from Bombyx mori, which uses a target-primed reverse transcription (TPRT) mechanism, but their distinct phylogeny suggests PLEs may utilize a novel mechanism of mobilization. Using protein purified from E. coli, we report unique in vitro properties of a PLE from the green anole (Anolis carolinensis), revealing mechanistic aspects not shared by other retrotransposons. We found that reverse transcription is initiated at two adjacent sites within the transposon RNA that is not homologous to the cleaved DNA, a feature that is reflected in the genomic \"tail\" signature shared between and unique to PLEs. Our results for the first active PLE in vitro provide a starting point for understanding PLE mobilization and biology.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"12"},"PeriodicalIF":4.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-05-10DOI: 10.1186/s13100-024-00321-0
Beverly Ann G Boyboy, Kenji Ichiyanagi
{"title":"Insertion of short L1 sequences generates inter-strain histone acetylation differences in the mouse.","authors":"Beverly Ann G Boyboy, Kenji Ichiyanagi","doi":"10.1186/s13100-024-00321-0","DOIUrl":"10.1186/s13100-024-00321-0","url":null,"abstract":"<p><strong>Background: </strong>Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence.</p><p><strong>Results: </strong>In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3' fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3' L1 fragments were hypoacetylated, suggesting a general activity of the 3' L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3' region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression.</p><p><strong>Conclusions: </strong>This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"15 1","pages":"11"},"PeriodicalIF":4.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11084082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}