Transcription factor OTX2 silences the expression of cleavage embryo genes and transposable elements.
Ontology highlight
ABSTRACT:
SUBMITTER: Guo SM
PROVIDER: S-EPMC8238675 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:During mammalian preimplantation development, stimulation of zygotic genome activation (ZGA) and transposable elements (TEs) shapes totipotency profiling. A rare mouse embryonic stem cells (mESCs) subpopulation is capable of transiently entering a state resembling 2-cell stage embryos, with subtypes of TEs expressed and ZGA genes transiently activated. In this study, we found that deletion of H2A.X in mESCs led to a significant upregulation of ZGA genes and misregulated TEs. ChIP-seq analysis indicated a direct association of H2A.X at the Dux locus for silencing the Dux gene and its downstream ZGA genes in mESCs. We also demonstrated that histone variant H2A.X is highly enriched in human cleavage embryos when ZGA genes and TEs are active. Therefore, we propose that H2A.X plays an important role in regulating ZGA genes and TEs to establish totipotency.
| S-EPMC8568613 | biostudies-literature
Project description:Transposable elements (TEs) contribute to gene expression regulation by acting as cis-regulatory elements that attract transcription factors and epigenetic regulators. This research aims to explore the functional and clinical implications of transposable element-related molecular events in hepatocellular carcinoma, focusing on the mechanism through which liver-specific accessible TEs (liver-TEs) regulate adjacent gene expression. Our findings reveal that the expression of HNF4A is inversely regulated by proximate liver-TEs, which facilitates liver cancer cell proliferation. Mechanistically, liver-TEs are predominantly occupied by the histone demethylase, KDM1A. KDM1A negatively influences the methylation of histone H3 Lys4 (H3K4) of liver-TEs, resulting in the epigenetic silencing of HNF4A expression. The suppression of HNF4A mediated by KDM1A promotes liver cancer cell proliferation. In conclusion, this study uncovers a liver-TE/KDM1A/HNF4A regulatory axis that promotes liver cancer growth and highlights KDM1A as a promising therapeutic target. Our findings provide insight into the transposable element-related molecular mechanisms underlying liver cancer progression.
| S-EPMC11224304 | biostudies-literature
Project description:BackgroundTransposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers.ResultsWe analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development.ConclusionsTE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development.
| S-EPMC6873666 | biostudies-literature
Project description:DNA methylation is a major silencing mechanism of transposable elements (TEs). Here we report that TEX15, a testis-specific protein, is required for TE silencing. TEX15 is expressed in embryonic germ cells and functions during genome-wide epigenetic reprogramming. The Tex15 mutant exhibits DNA hypomethylation in TEs at a level similar to Mili and Dnmt3c but not Miwi2 mutants. TEX15 is associated with MILI in testis. As loss of Tex15 causes TE desilencing with intact piRNA production, our results identify TEX15 as a new essential epigenetic regulator that may function as a nuclear effector of MILI to silence TEs by DNA methylation.
| S-EPMC7263141 | biostudies-literature
Project description:Transposable elements are powerful agents of evolution that can diversify transcriptional programs by distributing transcription factor DNA-binding sites throughout genomes. To investigate the extent that transposable elements provide transcription factor-binding motifs in Caenorhabditis elegans, we determined the genomic positions of DNA-binding motifs for 201 different transcription factors. Surprisingly, we found that almost all examined transcription factors have binding motifs that reside within transposable elements, and all types of transposable elements have at least 1 instance of a transcription factor motif, demonstrating that transposable elements provide previously unappreciated numbers of transcription factor-binding motifs to the C. elegans genome. After determining the occurrence of transcription factor motifs in transposable elements relative to the rest of the genome, we identified DNA-binding motifs for 45 different transcription factors that are greater than 20-fold enriched within transposable elements compared to what would be expected by chance. Consistent with potential functional roles for these transposable element-enriched transcription factor-binding sequences, we determined that all transcription factor motif types found in transposable elements have instances of residing within accessible chromatin sites associated with transcription factor binding. The overwhelming majority of transcription factor-binding motifs located within transposable elements associate with their cognate transcription factors, suggesting extensive binding of transcription factors to sequences within transposable elements. In addition, transposable elements with accessible or transcription factor-bound motifs reside in the putative promoter regions of approximately 12% of all protein-coding genes, providing widespread possibilities for influencing gene expression. This work represents the first comprehensive analysis of transposable element-transcription factor interactions in C. elegans and demonstrates that transposable element-provided transcription factor-binding sites are prevalent in this important model organism.
| S-EPMC8896005 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. DNA methylation is a major silencing mechanism of transposable elements (TEs). Here we report that TEX15, a testis-specific protein, is required for TE silencing. TEX15 is both cytoplasmic and nuclear in embryonic germ cells and functions during genome-wide epigenetic reprogramming. Tex15 mutant exhibits DNA hypomethylation in TEs at a level similar to Mili but not Miwi2 mutant. As loss of Tex15 causes TE de-silencing without abolishing piRNA production, our results identify TEX15 as a new essential epigenetic regulator that appears to function independently or downstream of the piRNA biogenesis machineries to silence TEs by DNA methylation in male germ cells.
2020-05-18 | GSE140571 | GEO
Project description:In the past, reactive nitrogen species (RNS) were supposed to be stress-induced by-products of disturbed metabolism that cause oxidative damage to biomolecules. However, emerging evidence demonstrates a substantial role of RNS as endogenous signals in eukaryotes. In plants, S-nitrosoglutathione (GSNO) is the dominant RNS and serves as the •NO donor for S-nitrosation of diverse effector proteins. Remarkably, the endogenous GSNO level is tightly controlled by S-nitrosoglutathione reductase (GSNOR) that irreversibly inactivates the glutathione-bound NO to ammonium. Exogenous feeding of diverse RNS, including GSNO, affected chromatin accessibility and transcription of stress-related genes, but the triggering function of RNS on these regulatory processes remained elusive. Here, we show that GSNO reductase-deficient plants (gsnor1-3) accumulate S-adenosylmethionine (SAM), the principal methyl donor for methylation of DNA and histones. This SAM accumulation triggered a substantial increase in the methylation index (MI = [SAM]/[S-adenosylhomocysteine]), indicating the transmethylation activity and histone methylation status in higher eukaryotes. Indeed, a mass spectrometry-based global histone profiling approach demonstrated a significant global increase in H3K9me2, which was independently verified by immunological detection using a selective antibody. Since H3K9me2-modified regions tightly correlate with methylated DNA regions, we also determined the DNA methylation status of gsnor1-3 plants by whole-genome bisulfite sequencing. DNA methylation in the CG, CHG, and CHH contexts in gsnor1-3 was significantly enhanced compared to the wild type. We propose that GSNOR1 activity affects chromatin accessibility by controlling the transmethylation activity (MI) required for maintaining DNA methylation and the level of the repressive chromatin mark H3K9me2.
| S-EPMC8301139 | biostudies-literature
Project description:Transposable elements are one of the main drivers of plant genome evolution. Transposon insertions can modify the gene coding capacity or the regulation of their expression, the latter being a more subtle effect, and therefore particularly useful for evolution. Transposons have been show to contain transcription factor binding sites that can be mobilized upon transposition with the potential to integrate new genes into transcriptional networks. Miniature inverted-repeat transposable elements (MITEs) are a type of noncoding DNA transposons that could be particularly suited as a vector to mobilize transcription factor binding sites and modify transcriptional networks during evolution. MITEs are small in comparison to other transposons and can be excised, which should make them less mutagenic when inserting into promoters. On the other hand, in spite of their cut-and-paste mechanisms of transposition, they can reach very high copy numbers in genomes. We have previously shown that MITEs have amplified and redistributed the binding motif of the E2F transcription factor in different Brassicas. Here, we show that MITEs have amplified and mobilized the binding motifs of the bZIP60 and PIF3 transcription factors in peach and Prunus mume, and the TCP15/23 binding motif in tomato. Our results suggest that MITEs could have rewired new genes into transcriptional regulatory networks that are responsible for important adaptive responses and breeding traits in plants, such as stress responses, flowering time, or fruit ripening. The results presented here therefore suggest a general impact of MITEs in the evolution of transcriptional regulatory networks in plants.
| S-EPMC5950925 | biostudies-literature
Project description:Transposable elements (TEs) have been associated with many, frequently detrimental, biological roles. Consequently, the regulations of TEs, e.g. via DNA-methylation and histone modifications, are considered critical for maintaining genomic integrity and other functions. Still, the high-throughput study of TEs is usually limited to the family or consensus-sequence level because of alignment problems prompted by high-sequence similarities and short read lengths. To entirely comprehend the effects and reasons of TE expression, however, it is necessary to assess the TE expression at the level of individual instances. Our simulation study demonstrates that sequence similarities and short read lengths do not rule out the accurate assessment of (differential) expression of TEs at the instance-level. With only slight modifications to existing methods, TE expression analysis works surprisingly well for conventional paired-end sequencing data. We find that SalmonTE and Telescope can accurately tally a considerable amount of TE instances, allowing for differential expression recovery in model and non-model organisms.
| S-EPMC8769692 | biostudies-literature
Project description:Transposable elements (TEs) are prevalent repeats in the human genome, play a significant role in the regulome, and their disruption can contribute to tumorigenesis. However, TE influence on gene expression in cancer remains unclear. Here, we analyze 275 normal colon and 276 colorectal cancer samples from the SYSCOL cohort, discovering 10,231 and 5,199 TE-expression quantitative trait loci (eQTLs) in normal and tumor tissues, respectively, of which 376 are colorectal cancer specific eQTLs, likely due to methylation changes. Tumor-specific TE-eQTLs show greater enrichment of transcription factors, compared to shared TE-eQTLs suggesting specific regulation of their expression in tumor. Bayesian networks reveal 1,766 TEs as mediators of genetic effects, altering the expression of 1,558 genes, including 55 known cancer driver genes and show that tumor-specific TE-eQTLs trigger the driver capability of TEs. These insights expand our knowledge of cancer drivers, deepening our understanding of tumorigenesis and presenting potential avenues for therapeutic interventions.
| S-EPMC10811328 | biostudies-literature