RNA-seq analysis about Lx8-SINE B2 knocked down samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182247 | GEO | 2022/09/19
REPOSITORIES: GEO
Similar Datasets
Project description:Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28,270 SINE loci, with ~50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.
2016-10-31 | GSE85518 | GEO
Project description:We report the comparison between SINE B2-AS transcriptome profiling and Dicer1-deficient-cell transcriptome profiling using RNA-seq analysis. We report that thousands of SINE B2 copies encode long B2-AS transcripts, which are constantly degraded by Dicer1. This new class of B2-AS transcripts regulates the expression of SINE B2 sense (B2-S) transcripts. Long B2-S is the main cause of cellular toxicity likely mediated by the multifunctional protein TSPO. Some B2-AS transcripts are putative miRNAs interconnected with the RNAi system. We propose that B2-AS transcripts have evolved as a self-defense mechanism to subvert the host RNAi system.
2020-09-01 | GSE126041 | GEO
Project description:Six methyltransferases divide labor in establishing genomic profiles of histone H3 lysine 9 methylation (H3K9me), an epigenomic modification involved in the formation of constitutive heterochromatin, gene repression and silencing of retroelements. Among them, SETDB1 is recruited to active chromatin compartments to silence the expression of endogenous retroviruses. In the context of experiments aimed at determining the role of SETDB1 in stimulus-inducible gene expression in macrophages, we unexpectedly found that upon SETDB1 depletion, loss of H3K9me3 in active compartments was associated with increased recruitment of CTCF to >1,600 DNA-binding motifs contained within SINE-B2 repeats, a previously unidentified target of SETDB1-mediated repression. CTCF is an essential regulator of chromatin folding that restrains DNA looping by cohesin, thus creating boundaries among adjacent topological domains. Increased CTCF binding to SINE-B2 repeats generated novel boundaries within topological domains containing lipopolysaccharide-inducible genes, correlating with their impaired regulation in response to stimulation. These data indicate a role of H3K9me3 in restraining genomic distribution and activity of CTCF, with impact on chromatin organization and gene regulation.
2022-03-31 | GSE189973 | GEO
Project description:More than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates return to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi with amyloid pathology and in an in vitro cell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD).
2020-11-19 | GSE149243 | GEO
Project description:Six methyltransferases divide labor in establishing genomic profiles of histone H3 lysine 9 methylation (H3K9me), an epigenomic modification involved in the formation of constitutive heterochromatin, gene repression and silencing of retroelements. Among them, SETDB1 is recruited to active chromatin compartments to silence the expression of endogenous retroviruses. In the context of experiments aimed at determining the role of SETDB1 in stimulus-inducible gene expression in macrophages, we unexpectedly found that upon SETDB1 depletion, loss of H3K9me3 in active compartments was associated with increased recruitment of CTCF to >1,600 DNA-binding motifs contained within SINE-B2 repeats, a previously unidentified target of SETDB1-mediated repression. CTCF is an essential regulator of chromatin folding that restrains DNA looping by cohesin, thus creating boundaries among adjacent topological domains. Increased CTCF binding to SINE-B2 repeats generated novel boundaries within topological domains containing lipopolysaccharide-inducible genes, correlating with their impaired regulation in response to stimulation. These data indicate a role of H3K9me3 in restraining genomic distribution and activity of CTCF, with impact on chromatin organization and gene regulation.
2022-03-31 | GSE189971 | GEO
Project description:Six methyltransferases divide labor in establishing genomic profiles of histone H3 lysine 9 methylation (H3K9me), an epigenomic modification involved in the formation of constitutive heterochromatin, gene repression and silencing of retroelements. Among them, SETDB1 is recruited to active chromatin compartments to silence the expression of endogenous retroviruses. In the context of experiments aimed at determining the role of SETDB1 in stimulus-inducible gene expression in macrophages, we unexpectedly found that upon SETDB1 depletion, loss of H3K9me3 in active compartments was associated with increased recruitment of CTCF to >1,600 DNA-binding motifs contained within SINE-B2 repeats, a previously unidentified target of SETDB1-mediated repression. CTCF is an essential regulator of chromatin folding that restrains DNA looping by cohesin, thus creating boundaries among adjacent topological domains. Increased CTCF binding to SINE-B2 repeats generated novel boundaries within topological domains containing lipopolysaccharide-inducible genes, correlating with their impaired regulation in response to stimulation. These data indicate a role of H3K9me3 in restraining genomic distribution and activity of CTCF, with impact on chromatin organization and gene regulation.
2022-03-31 | GSE189970 | GEO
Project description:Six methyltransferases divide labor in establishing genomic profiles of histone H3 lysine 9 methylation (H3K9me), an epigenomic modification involved in the formation of constitutive heterochromatin, gene repression and silencing of retroelements. Among them, SETDB1 is recruited to active chromatin compartments to silence the expression of endogenous retroviruses. In the context of experiments aimed at determining the role of SETDB1 in stimulus-inducible gene expression in macrophages, we unexpectedly found that upon SETDB1 depletion, loss of H3K9me3 in active compartments was associated with increased recruitment of CTCF to >1,600 DNA-binding motifs contained within SINE-B2 repeats, a previously unidentified target of SETDB1-mediated repression. CTCF is an essential regulator of chromatin folding that restrains DNA looping by cohesin, thus creating boundaries among adjacent topological domains. Increased CTCF binding to SINE-B2 repeats generated novel boundaries within topological domains containing lipopolysaccharide-inducible genes, correlating with their impaired regulation in response to stimulation. These data indicate a role of H3K9me3 in restraining genomic distribution and activity of CTCF, with impact on chromatin organization and gene regulation.
2022-03-31 | GSE189974 | GEO
Project description:Mouse SINE B2 elements function as IFN-inducible enhancer elements
| PRJNA836589 | ENA
Project description:More than 98% of the mammalian genome is noncoding and approximately half is made up of transposable elements. One of the most abundant is the short interspersed nuclear elements (SINE). Among the million copies of SINEs, B2 accounts for ~350,000 in the mouse genome and have garnered special interest because of emerging roles in gene regulation. Our recent work demonstrated that B2 RNA normally binds stress genes to retard transcription elongation. Though epigenetically silenced, B2s become massively upregulated during thermal stress. Specifically, an interaction between B2 RNA and the Polycomb protein, EZH2, results in cleavage of B2 RNA, release of B2 RNA from RNA Polymerase II, and activation of the stress genes. Although an established RNA-binding protein and histone methyltransferase, EZH2 is not known to be a nuclease. Here, we provide evidence for the surprising conclusion that B2 is a self-cleaving RNA. Contact with EZH2 accelerates cleavage rate by >100-fold, suggesting that EZH2 may assist cleavage as an RNA chaperone. Modification-interference analysis demonstrate that phosphorothioate changes at A and C nucleotides can substitute for EZH2’s function. B2 mutagenesis indicate that nucleotides around positions 45-55 and 100-101 are critical for cleavage reaction. Finally, we demonstrate that another family of SINEs, the ALU elements produce also a self-cleaving RNA. ALUs are intrinsically more auto-reactive than B2s. We propose that the B2/ALU SINEs are a new class of ribozymes whose activity is accelerated by EZH2.
2020-01-31 | GSE139931 | GEO
Project description:Mouse SINE B2 elements function as IFN-inducible enhancer elements [RNA-Seq]
| PRJNA836593 | ENA