Analysis of DNA methylation dynamics at Alu elements during human B cell activation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42386 | GEO | 2013/03/01
SECONDARY ACCESSION(S): PRJNA181260
REPOSITORIES: GEO
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Project description:Paired-end sequencing of methylated DNA fragments in B cell subsets revealed widespread loss of methylation at Alu elements upon B cell activation. DNA methylation pattern was analyzed in purified naïve and germinal-center B cells derived from 1 patient
2013-03-01 | E-GEOD-42386 | biostudies-arrayexpress
Project description:Weaker CEBPA binding in the human than in the mouse genome is a general trait of the human genome across multiple biological conditions. Alu repeats carry strong CEBPA binding motifs, which compete with regulatory regions for CEBPA binding. To directly test this hypothesis, we attempted to overcome Alu competition by using, first, a CRISPR-dCas9 system in BLaER1 cells (Rapino et al. 2013). By promoting the recruitment of the inactive Cas9 to Alu regions with specific gRNAs targeting Alu repeats containing strong CEBPA motifs we protected them, hampering CEBPA binding to these regions. We tested the effect of two different paired gRNA constructs in two replicates and one control paired gRNA in two replicates. Second, we also further overexpressed CEBPA in human BLaER1 cells to overcome Alu competition. We tested two doses of CEBPA overexpression in two replicates and one control experiment in two replicates.
2023-05-01 | E-MTAB-12597 | biostudies-arrayexpress
Project description:Folding of the mammalian genome is governed by architectural proteins, such asCTCF. TFIIIC, a RNA polymerase III transcription factor, has been identified as aninsulator but its role in genome topology is totally unknown. Here, we show that TFIIICestablishes long-range genomic interactions that affect gene expression. Upon serumstarvation (SS), TFIIIC occupancy increases at Alu elements (AEs) near promoters ofcell cycle-related genes. Bound AEs become H3K18 hyper-acetylated and fold tocontact distal pre-loaded CTCF sites near other cell cycle genes. The promoters ofthese genes also become hyper-acetylated ensuring their basal transcription during SSand their increased expression during serum re-exposure. Ablation of TFIIIC ordeletion of the TFIIIC-bound AE that loops to the G2/M cycling F (CCNF) locus affectsits expression and nuclear positioning. These results illustrate a novel function ofhuman TFIIIC in changing 3D genome topology through the epigenetic state of AEs.
2020-05-26 | PXD011250 | Pride
Project description:An extrachromosomal replication system was established to examine the perturbation of Alu-carrying genes in response to elevated Alu RNAs in the opposite direction. The null hypothesis is that the Alu-carrying RNA duplex cannot trigger subsequent post-transcriptional regulation, manifesting a random perturbation of expression levels. Comparing HEK293 cells transfected and not-transfected with pDR2-Alu vectors.
2013-05-13 | E-GEOD-39822 | biostudies-arrayexpress
Project description:Alu element is a major contributor to lineage-specific new exons in the primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements (such as Alu) are restricted to regulatory functions but do not have adequate evolutionary time to be incorporated into stable, functional proteins. In this work, we adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and mass spectrometry data of diverse human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances even between humans and closely related nonhuman primates. In the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA editing analyses of RNA-sequencing data demonstrate that both the Alu exon skipping and inclusion isoforms encode active RNA editing enzymes, while the Alu exon peptide may fine tune the editing activities of the ADARB1 protein products . Together, our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution. Comparing the A-I RNA editing levels during HEK293 (control), ADARB1 long isoform (with Alu exon) transfected, and short isoform (without Alu exon) transfected cells, each group has 3 replicates.
2015-12-10 | E-GEOD-65999 | biostudies-arrayexpress
Project description:An extrachromosomal replication system was established to examine the perturbation of Alu-carrying genes in response to elevated Alu RNAs in the opposite direction. The null hypothesis is that the Alu-carrying RNA duplex cannot trigger subsequent post-transcriptional regulation, manifesting a random perturbation of expression levels.
2013-05-13 | GSE39822 | GEO
Project description:Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the role of Alu has not been studied comprehensively in brain tumor because an evolutionary perspective has been the subject of little research in brain tumor. We aim to investigate the relevance of Alu to the gliomagenesis.
2021-01-27 | GSE165595 | GEO
Project description:Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RIC-seq technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs in HeLa cells. Here, we apply this technology to generate high-confidence enhancer-promoter RNA interaction (EPRI) maps in six additional cell lines. Using these maps, we discover that 37.9% of the enhancer-promoter RNA interaction sites are overlapped with Alu sequences. These pairwise interacting Alu and non-Alu RNA sequences tend to be complementary and potentially form duplexes. Knockout of Alu elements compromises enhancer-promoter looping, whereas Alu insertion or CRISPR-dCasRx-mediated Alu tethering to unregulated promoter RNAs can create new loops to homologous enhancers. Importantly, mapping 535,404 noncoding risk variants back to the EPRI maps enabled us to construct variant-to-function maps for interpreting their molecular functions, including 15,318 deletions or insertions in 11,677 Alu elements that affect 6,497 protein-coding genes. We further demonstrate that polymorphic Alu insertion at PTK2 enhancer can promote tumorigenesis. Our study uncovers a principle for determining enhancer-promoter pairing specificity and provides a framework to link noncoding risk variants to their molecular functions.
2023-05-11 | GSE190214 | GEO
Project description:To identify the genome-wide impact of Alu/Alu-mediated rearrangement (AAMR) on variation and human health, we have developed a bioinformatic approach to characterize Alus involved in mediating CNVs and have predicted genome-wide AAMR hotspot loci. This prediction was validated by performing molecular biological experiments on 89 samples selected by correlating AAMR hotspot genes with a database of ~54,000 chromosomal microarrays.
2017-06-29 | GSE100590 | GEO
Project description:Alu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products. Our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution.
2015-12-10 | GSE65999 | GEO