High-throughput discovery of post-transcriptional cis-regulatory elements
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PROVIDER: PRJNA302654 | ENA |
REPOSITORIES: ENA
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Project description:Post-transcriptional gene regulation controls the amount of a protein produced from an individual mRNA transcript by altering mRNA decay and translation rates. Many putative post-transcriptional cis-regulatory elements have been identified from computational, molecular biology, and biochemical studies studies; however, identifying which sequence elements are sufficient to regulate expression remains challenging. We created a high-throughput, cell-based screen that tested the post-transcriptional regulatory potential for thousands of short sequence elements. Sequences with known effects have the expected performance in this screen, showing this methodology is robust. Hundreds of novel short sequences were identified as being able to alter gene expression, both by increasing and decreasing protein production from the fluorescence reporter, and we validated the effects for fifty of these sequences. Importantly, sequences discovered in this screen are conserved in human 3′UTRs, and furthermore, the sequences can regulate expression in the context of those endogenous 3′UTRs. Hundreds of previously unknown post-transcriptional cis-regulatory elements exist, many of which increase gene expression. These results suggest that each human 3′UTR has many small cis-regulatory elements that interact with RNA binding proteins, and these interactions control the fate of an mRNA transcript.
2016-03-07 | GSE75136 | GEO
Project description:Post-transcriptional gene regulation controls the amount of a protein produced from an individual mRNA transcript by altering mRNA decay and translation rates. Many putative post-transcriptional cis-regulatory elements have been identified from computational, molecular biology, and biochemical studies studies; however, identifying which sequence elements are sufficient to regulate expression remains challenging. We created a high-throughput, cell-based screen that tested the post-transcriptional regulatory potential for thousands of short sequence elements. Sequences with known effects have the expected performance in this screen, showing this methodology is robust. Hundreds of novel short sequences were identified as being able to alter gene expression, both by increasing and decreasing protein production from the fluorescence reporter, and we validated the effects for fifty of these sequences. Importantly, sequences discovered in this screen are conserved in human 3?UTRs, and furthermore, the sequences can regulate expression in the context of those endogenous 3?UTRs. Hundreds of previously unknown post-transcriptional cis-regulatory elements exist, many of which increase gene expression. These results suggest that each human 3?UTR has many small cis-regulatory elements that interact with RNA binding proteins, and these interactions control the fate of an mRNA transcript.
2016-03-07 | GSE75135 | GEO
Project description: Not available
| S-EPMC4778349 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-03-04 | GSE75161 | GEO
Project description:High-throughput discovery of post-transcriptional cis-regulatory elements (miRNA-seq)
| PRJNA302653 | ENA
Project description:High-throughput discovery of post-transcriptional cis-regulatory elements (8-nt)
| PRJNA302651 | ENA
Project description:Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements, contribute to cancer pathophysiology largely due to lack of high throughput assays to assess their functional effects. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants in human hematopoietic malignancies by combining targeted resequencing, mutation discovery, CRISPR-based enhancer-selective epigenome editing, and enhancer reporter assays. We identify 4,629 recurrent non-coding alterations and 939 mutation-associated pathogenic enhancers controlling proto-oncogenes or tumor suppressors. Enhancer variants at KRAS and PER2 co-localize with nuclear receptor (NR) binding sites and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently associate with non-coding variants across cancer types. Hence, recurrent non-coding somatic variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.
2020-04-22 | GSE125939 | GEO
Project description:Chromatin boundary elements contribute to the partitioning of mammalian genomes into topological domains to regulate gene expression. Certain boundary elements are adopted as DNA insulators for safe and stable transgene expression in mammalian cells. These elements, however, are ill-defined and less characterized in the non-coding genome, partially due to the lack of a platform to readily evaluate boundary-associated activities of putative DNA sequences. Here we report SHIELD (Site-specific Heterochromatin Insertion of Elements at Lamina-associated Domains), a novel platform tailored for the high-throughput screening of barrier-type DNA elements in human cells. SHIELD takes advantage of the high specificity of serine integrase at heterochromatin, and exploits the natural heterochromatin spreading inside LADs for the discovery of potent barrier elements. We adopted SHIELD to evaluate the barrier activity of 1000 DNA elements in a high-throughput manner and identified 8 novel elements with barrier activities comparable to the core region of cHS4 element. SHIELD should greatly facilitate the discovery of novel barrier DNA elements from the non-coding genome in human cells.
2023-08-01 | GSE236198 | GEO
Project description:Decoding post-transcriptional regulatory programs underlying gene expression is a crucial step toward a predictive dynamical understanding of cellular state transitions. Despite recent systematic efforts, the sequence determinants of such mechanisms remain largely uncharacterized. An important obstacle in revealing these elements stems from the contribution of local secondary structures in defining interaction partners in a variety of regulatory contexts, including but not limited to transcript stability, alternative splicing and localization. There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (e.g. human cardiac troponin T) or affects other aspects of RNA biology. Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence. We have developed a computational framework based on context-free grammars and mutual information that systematically explores the immense space of structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behavior. The application of this framework to genome-wide mammalian mRNA stability data revealed eight highly significant elements with substantial structural information, for the strongest of which we showed a major role in global mRNA regulation. Through biochemistry, mass-spectrometry, and in vivo binding studies, we identified HNRPA2B1 as the key regulator that binds this element and stabilizes a large number of its target genes. Ultimately, we created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach can also be employed to reveal the structural elements that modulate other aspects of RNA behavior. This SuperSeries is composed of the following subset Series: GSE35749: sRSM1 synthetic decoy vs. scrambled transfections in MDA-MB-231 cells GSE35753: HNRPA2B1 RIP-chip GSE35756: Whole-genome decay rate measurements in MDA-MB-231 cells transfected with HNRPA2B1 siRNAs versus controls GSE35757: siRNA-mediated HNRPA2B1 knock-down in MDA-MB-231 cells GSE35799: HNRPA2B1 HITS-CLIP Refer to individual Series
2012-02-28 | E-GEOD-35800 | biostudies-arrayexpress
Project description:Genome-wide discovery of daily transcriptome, cis-regulatory elements and transcription factor footprints in the monarch butterfly brain
| PRJNA505259 | ENA