Ultraconserved elements in Rhabditidae and Panagrolaimidae
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PROVIDER: PRJEB90354 | ENA |
REPOSITORIES: ENA
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Project description:The manuscript by D. Licastro and colleagues “Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements” presents an overview of experimental and computational approaches employed by the authors to perform a multi-facet characterization of ultraconserved elements (UCEs). The authors present an interesting analysis where they investigate the transcription of UCEs in mouse development at different stages by conductin an microarray experiment. Some of these results are further verified by RT-PCR. 12 Samples, 4 groups 3 samples per group.
2010-06-16 | E-GEOD-19371 | biostudies-arrayexpress
Project description:The manuscript by D. Licastro and colleagues “Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements” presents an overview of experimental and computational approaches employed by the authors to perform a multi-facet characterization of ultraconserved elements (UCEs). The authors present an interesting analysis where they investigate the transcription of UCEs in mouse development at different stages by conductin an microarray experiment. Some of these results are further verified by RT-PCR.
2010-06-16 | GSE19371 | GEO
Project description:Non-coding ultraconserved regions showing hundreds of consecutive bases of perfect evolutionary sequence conservation across mammalian genomes have intrigued biologists in the decade since they were first described. While many of these sequences are known to represent distant-acting enhancers, initial deletion studies in mice showed that their loss had no obvious impact on viability or fertility. To explore the discrepancy between extraordinary evolutionary constraint and an apparent lack of phenotypes when deleted in vivo, we used genome editing to create an expanded series of knockout mice lacking individual or combinations of ultraconserved brain enhancers near the essential neuronal transcription factor Arx. While the loss of any single or pair of ultraconserved enhancers resulted in viable and fertile mice, detailed phenotyping revealed neurological or growth abnormalities in nearly all cases, including substantial alterations of neuron populations and abnormalities of the dentate gyrus. Our results demonstrate the functional importance of ultraconserved enhancers and highlight that extreme sequence conservation may result from evolutionary selection against fitness deficits that appear subtle in a laboratory setting.
2018-01-17 | GSE100384 | GEO
Project description:Analysis of the transcriptional changes in the forebrain resulting from the loss of ultraconserved enhancers near Arx gene.
2018-01-17 | GSE97321 | GEO
Project description:In this study, we identified the dysregulated ultraconserved regions (UCRs) in Non-small-Cell Lung Cancer patients. We measured the expression profile of UCRs in 18 paired frozen tumor and adjacent non-tumor lung, by microarray analysis. This analysis is performed to identify the most significant dysregulated T-UCRs in tumor compared to the near non-cancerous lung tissue.
2021-12-07 | E-MTAB-11010 | biostudies-arrayexpress
Project description:BackgroundOligodendrocytes are specialized cells of the nervous system that produce the myelin sheaths surrounding the axons of neurons. Myelinating the axons increases the speed of nerve conduction and demyelination contributes to the pathology of neurodegenerative diseases such as multiple sclerosis. Oligodendrocyte differentiation is specified early in development by the expression of the basic-helix-loop-helix transcription factor Olig2 in the ventral region of the neural tube. Understanding how Olig2 expression is controlled is therefore essential for elucidating the mechanisms governing oligodendrocyte differentiation. A method is needed to identify potential regulatory sequences in the long stretches of adjacent non-coding DNA that flank Olig2.Methodology/principal findingsWe identified ten potential regulatory regions upstream of Olig2 based on a combination of bioinformatics metrics that included evolutionary conservation across multiple vertebrate genomes, the presence of potential transcription factor binding sites and the existence of ultraconserved elements. One of our computational predictions includes a region previously identified as the Olig2 basal promoter, suggesting that our criterion represented characteristics of known regulatory regions. In this study, we tested one candidate regulatory region for its ability to modulate the Olig2 basal promoter and found that it represses expression in undifferentiated embryonic stem cells.Conclusions/significanceThe regulatory region we identified modifies the expression regulated by the Olig2 basal promoter in a manner consistent with our current understanding of Olig2 expression during oligodendrocyte differentiation. Our results support a model in which constitutive activation of Olig2 by its basal promoter is repressed in undifferentiated cells by upstream repressive elements until that repression is relieved during differentiation. We conclude that the potential regulatory elements presented in this study provide a good starting point for unraveling the cis-regulatory logic that governs Olig2 expression. Future studies of the functionality of the potential regulatory elements we present will help reveal the interactions that govern Olig2 expression during development.
| S-EPMC2596485 | biostudies-literature
Project description:We investigate the role of a long ncRNA transcribed from an ultraconserved region (T-UCR) in the control of post-transcriptional pri-miRNA processing. The regulation is based on complementarity between the lower stem region in pri-miR-195 transcript and the ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In this work, we characterize a new role for Uc.283+A as a direct interactor and regulator of pri-miRNA-195 maturation at the level of Drosha processing. We combine cellular assays with in vitro biochemical analyses to reveal the first case of RNA-directed downregulation of miRNA biogenesis by a T-UCR
2014-05-01 | GSE56841 | GEO
Project description:Ultraconserved elements were discovered two decades ago, arbitrarily defined as sequences that are identical over a length ≥ 200 bp in the human, mouse, and rat genomes. The definition was subsequently extended to sequences ≥ 100 bp identical in at least three of five mammalian genomes (including dog and cow), and shown to have undergone rapid expansion from ancestors in fish and strong negative selection in birds and mammals. Since then, many more genomes have become available, allowing better definition and more thorough examination of ultraconserved element distribution and evolutionary history. We developed a fast and flexible analytical pipeline for identifying ultraconserved elements in multiple genomes, dedUCE, which allows manipulation of minimum length, sequence identity, and number of species with a detectable ultraconserved element according to specified parameters. We suggest an updated definition of ultraconserved elements as sequences ≥ 100 bp and ≥97% sequence identity in ≥50% of placental mammal orders (12,813 ultraconserved elements). By mapping ultraconserved elements to ∼200 species, we find that placental ultraconserved elements appeared early in vertebrate evolution, well before land colonization, suggesting that the evolutionary pressures driving ultraconserved element selection were present in aquatic environments in the Cambrian-Devonian periods. Most (>90%) ultraconserved elements likely appeared after the divergence of gnathostomes from jawless predecessors, were largely established in sequence identity by early Sarcopterygii evolution-before the divergence of lobe-finned fishes from tetrapods-and became near fixed in the amniotes. Ultraconserved elements are mainly located in the introns of protein-coding and noncoding genes involved in neurological and skeletomuscular development, enriched in regulatory elements, and dynamically expressed throughout embryonic development.
| S-EPMC11276968 | biostudies-literature
Project description:Ultraconserved (UCEs) are popular markers for phylogenomic studies. They are relatively simple to collect from distantly-related organisms, and contain sufficient information to infer relationships at almost all taxonomic levels. Most studies of UCEs use partitioning to account for variation in rates and patterns of molecular evolution among sites, for example by estimating an independent model of molecular evolution for each UCE. However, rates and patterns of molecular evolution vary substantially within as well as between UCEs, suggesting that there may be opportunities to improve how UCEs are partitioned for phylogenetic inference. We propose and evaluate new partitioning methods for phylogenomic studies of UCEs: Sliding-Window Site Characteristics (SWSC), and UCE Site Position (UCESP). The first method uses site characteristics such as entropy, multinomial likelihood, and GC content to generate partitions that account for heterogeneity in rates and patterns of molecular evolution within each UCE. The second method groups together nucleotides that are found in similar physical locations within the UCEs. We examined the new methods with seven published data sets from a variety of taxa. We demonstrate the UCESP method generates partitions that are worse than other strategies used to partition UCE data sets (e.g., one partition per UCE). The SWSC method, particularly when based on site entropies, generates partitions that account for within-UCE heterogeneity and leads to large increases in the model fit. All of the methods, code, and data used in this study, are available from https://github.com/Tagliacollo/PartitionUCE. Simplified code for implementing the best method, the SWSC-EN, is available from https://github.com/Tagliacollo/PFinderUCE-SWSC-EN.
| S-EPMC5995204 | biostudies-literature
Project description:Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.
| S-EPMC1964772 | biostudies-literature