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Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE19371 | GEO | 2010/06/16

SECONDARY ACCESSION(S): PRJNA120415

REPOSITORIES: GEO

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Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements

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

Mus musculus

Project description:Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements

| PRJNA120415 | ENA

Ultraconserved Enhancers Are Required for Normal Development [Drop-seq]

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.

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Project description:Analysis of the transcriptional changes in the forebrain resulting from the loss of ultraconserved enhancers near Arx gene.

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Transcriptional profiling of ultraconserved Regions in Lung Cancer patients

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.

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Transcribed ultraconserved region 339 promotes carcinogenesis by sequestering tumor suppressor microRNAs

Project description:The transcribed ultraconserved regions (T-UCRs) are a family of long non-coding RNAs implicated in human carcinogenesis. The mechanism of action of T-UCRs and the factors regulating their expression in human cancers are poorly understood. In this study we show that high expression of uc.339 correlates with lower survival in 204 non-small cell lung cancer (NSCLC) patients. We also show that uc.339 found up-regulated in archival NSCLC samples, functions as a decoy for miR-339-3p, -663-3p and -95-5p. As a result, Cyclin E2, a direct target of these microRNAs is up-regulated, promoting cancer growth and migration. We provide evidence from cell lines and primary samples suggesting that TP53 directly regulates uc.339. Our results support a key role for uc.339 in lung cancer.

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Differentially expressed Transcribed ultraconserved regions (T-UCRs) in Crohn's disease (CD) comparing to normal controls (NC)

Project description:To date, 481 transcribed ultraconserved regions (T-UCRs) have been discovered in human genome. We aimed to investigate their characteristics in Crohn’s disease (CD) with conparison to healthy normal controls, to reveal differentially expressed T-UCRs.

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Transcribed ultraconserved region 339 promotes carcinogenesis by sequestering tumor suppressor microRNAs

2015-07-07 | E-GEOD-70540 | biostudies-arrayexpress

The genome-wide dual-CRISPR screening identifies essential non-coding regulatory elements

Project description:Non-coding regulatory elements (NCRE) represent a major fraction of the human genome, play important roles in different biological pathways, and have the potential as genomic medicine targets. We developed a straightforward dual-CRISPR screening system capable of deleting thousands of NCREs genome-wide to study their functions in distinct biological contexts in K562 cells and 293T cells. We show that many NCREs, including ultraconserved elements (UCE), have silencer activity and play essential roles in cell growth and drug response. NCREs with redundant functions could also be identified from the screening data. This dual-CRISPR system is also compatible with single-cell sequencing. We identified that UCE PAX6_Tarzan might be critical in heart development, as removing it from human embryonic stem cells led to defects in cardiomyocyte differentiation. Our study provides further evidence that many NCREs have important biological functions contributing to human biology and diseases, and may serve as future drug targets.

2024-01-28 | GSE254241 | GEO

MicroRNA profiling of human cancer samples identifies ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.

Project description:A critical question in molecular oncology is how extensive is the involvement of non-codingRNAs (ncRNAs) in human tumorigenesis. Herein, we report that a large fraction of genomic ultraconserved regions (UCRs) are encoding a particular set of ncRNAs and are altered in human cancers. We show that UCRs are frequently located at fragile sites and genomic regions involved in cancers, and that genome-wide UCRs profiling reveals distinct signatures in human leukemias and carcinomas. We proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells, and we identified UCRs whose expression may be regulated by miRNAs abnormally expressed in human chronic lymphocytic leukemia (CLL). Our findings argue that non-coding genes are involved in tumorigenesis at a greater extent as thought before and offer the perspective of identification of signatures associated with diagnosis, prognosis and response to treatment composed by various categories of ncRNA genes.

2007-12-01 | E-TABM-184 | biostudies-arrayexpress

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