YY1 is a transcriptional activator of mouse LINE-1 Tf subfamily

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 4, 2024

Long interspersed element type 1 (LINE-1, L1) is an active autonomous transposable (TE) in the human genome. The first step of L1 replication transcription, which controlled by internal RNA polymerase II promoter 5' untranslated region (UTR) a full-length L1. It has been shown that transcription factor YY1 binds to conserved sequence motif at end 5'UTR and dictates where initiates but not level transcription. Putative YY1-binding motifs have predicted 5'UTRs two distinct mouse subfamilies, Tf Gf. Using site-directed mutagenesis, vitro binding, gene knockdown assays, we experimentally tested role Our results indicate Tf, Gf subfamily, harbors functional sites its monomers. In contrast L1, functions as transcriptional activator for subfamily. Furthermore, are solely responsible synergistic interaction between monomers, consistent with model wherein distant monomers act enhancers abundance elements also raise important implications regulation genomic level.

Language: Английский

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Transposable elements acquire time- and sex-specific transcriptional and epigenetic signatures along mouse fetal gonad development

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 11, 2024

Gonadal sex determination in mice is a complex and dynamic process, which crucial for the development of functional reproductive organs. The expression genes involved this process regulated by variety genetic epigenetic mechanisms. Recently, there has been increasing evidence that transposable elements (TEs), are class mobile elements, play significant role regulating gene during embryogenesis organ development. In study, we aimed to investigate involvement TEs regulation mouse embryonic gonadal Through bioinformatics analysis, identify characterize specific operate as regulatory sex-specific genes, well their potential mechanisms regulation. We identified TE loci expressed time- manner along fetal gonad correlate positively negatively with nearby expression, suggesting integrated network. Moreover, chromatin accessibility histone post-transcriptional modification analyses differentiating supporting cells revealed acquiring signature promoter-, enhancer-, silencer-like some them being proximal critical sex-determining genes. Altogether, our study introduces new players network controls mammals.

Language: Английский

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Unraveling the genetics of arsenic toxicity with cellular morphology QTL

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(4), P. e1011248 - e1011248

Published: April 25, 2024

The health risks that arise from environmental exposures vary widely within and across human populations, these differences are largely determined by genetic variation gene-by-environment (gene–environment) interactions. However, risk assessment in laboratory mice typically involves isogenic strains therefore, does not account for known effects. In this context, genetically heterogenous cell lines promising tools population-based screening because they provide a way to introduce without increasing animal use. Cell reference populations of offer diversity, power mapping, potentially, predictive value vivo experimentation matched individuals. To explore further, we derived panel fibroblast population (the Diversity Outbred, DO). We then used high-content imaging capture hundreds morphology traits cells exposed the oxidative stress-inducing arsenic metabolite monomethylarsonous acid (MMA III ). employed dose-response modeling latent parameters response identify several hundred quantitative trait loci (cmQTL). Response cmQTL encompass genes with established associations cellular responses exposure, including Abcc4 Txnrd1 , as well novel gene candidates like Xrcc2 . Moreover, baseline highlight influence natural on fundamental aspects nuclear morphology. show variants influencing include both coding non-coding variation, haplotypes can be predict orthogonal lines. Our study sheds light major molecular initiating events stress under regulation, NRF2-mediated antioxidant response, detoxification pathways, DNA damage repair death trajectories.

Language: Английский

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YY1 is a transcriptional activator of the mouse LINE-1 Tf subfamily

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(21), P. 12878 - 12894

Published: Oct. 26, 2024

Abstract Long interspersed element type 1 (LINE-1, L1) is an active autonomous transposable in human and mouse genomes. L1 transcription controlled by internal RNA polymerase II promoter the 5′ untranslated region (5′UTR) of a full-length L1. It has been shown that factor YY1 binds to conserved sequence at end 5′UTR primarily dictates where initiates. Putative YY1-binding motifs have predicted 5′UTRs two distinct subfamilies, Tf Gf. Using site-directed mutagenesis, vitro binding gene knockdown assays, we experimentally tested role transcription. Our results indicate Tf, but not Gf subfamily, harbors functional sites monomers functions as transcriptional activator for subfamily. Activation during early embryogenesis also supported reanalysis published zygotic data. Furthermore, are solely responsible synergistic interaction between monomers, consistent with model wherein distant act enhancers The abundance elements raise important implications regulation across genome.

Language: Английский

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Interactions between microbiota and uterine corpus endometrial cancer: A bioinformatic investigation of potential immunotherapy

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0312590 - e0312590

Published: Oct. 30, 2024

Microorganisms in the gut and other niches may contribute to carcinogenesis while also altering cancer immune surveillance therapeutic response. However, determining impact of genetic variations interplay with intestinal microbes’ environment is difficult unanswered. Here, we examined frequency thirteen mutant genes that caused aberrant thirty different types using The Cancer Genomic Atlas (TCGA) database. Substantially, our findings show all these mutated are quite frequent uterine corpus endometrial (UCEC). Further, implicated infiltration subset cells within Tumor Microenvironment (TME) UCEC patients. top-ranking promote cell invasion into TME patients were PGLYRP2, OLFM4, TLR5. In this regard, used same deconvolution TCGA database analyze microbiome have a strong association Several bacteria viruses been linked cells, such as B memory T regulatory (Tregs), As result, pave way for future research generating novel immunizations against or immunotherapy

Language: Английский

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