The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme

2008 ◽  
Vol 389 (4) ◽  
pp. 323-331 ◽  
Author(s):  
David Umlauf ◽  
Peter Fraser ◽  
Takashi Nagano
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Chromatin Structure ◽  
Genome Architecture ◽  
Paradoxical Situation ◽  
Intergenic Regions ◽  
Non Coding Rnas ◽  
Variations On A Theme

Abstract Transcriptome studies have uncovered a plethora of non-coding RNAs (ncRNA) in mammals. Most originate within intergenic regions of the genome and recent evidence indicates that some are involved in many different pathways that ultimately act on genome architecture and gene expression. In this review, we discuss the role of well-characterized long ncRNAs in gene regulation pointing to their similarities, but also their differences. We will attempt to highlight a paradoxical situation in which transcription is needed to repress entire chromosomal domains possibly through the action of ncRNAs that create nuclear environments refractory to transcription.

Being in a loop: how long non-coding RNAs organise genome architecture

2019 ◽  
Vol 63 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Giuseppina Pisignano ◽  
Ioanna Pavlaki ◽  
Adele Murrell
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Potential Role ◽  
Conclusive Evidence ◽  
Genome Architecture ◽  
Chromatin Interactions ◽  
In Trans ◽  
Non Coding Rnas ◽  
Expression Evidence ◽  
In Cis

Abstract Chromatin architecture has a significant impact on gene expression. Evidence in the last two decades support RNA as an important component of chromatin structure [Genes Dev. (2005) 19, 1635–1655; PLoS ONE (2007) 2, e1182; Nat. Genet. (2002) 30, 329–334]. Long non-coding RNAs (lncRNAs) are able to control chromatin structure through nucleosome positioning, interaction with chromatin re-modellers and chromosome looping. These functions are carried out in cis at the site of lncRNAs transcription or in trans at distant loci. While the evidence for a role in lncRNAs in regulating gene expression through chromatin interactions is increasing, there is still very little conclusive evidence for a potential role in looping organisation. Here, we review models for the involvement of lncRNAs in genome architecture and the experimental evidence to support them.

ATRX in chromatin assembly and genome architecture during development and disease

2011 ◽  
Vol 89 (5) ◽  
pp. 435-444 ◽  
Author(s):  
Nathalie G. Bérubé
Keyword(s):  
Gene Regulation ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Higher Order ◽  
Chromatin Assembly ◽  
Genome Architecture ◽  
Chromatin Conformation ◽  
Mammalian Development ◽  
Mitosis And Meiosis

The regulation of genome architecture is essential for a variety of fundamental cellular phenomena that underlie the complex orchestration of mammalian development. The ATP-dependent chromatin remodeling protein ATRX is emerging as a key regulatory component of nucleosomal dynamics and higher order chromatin conformation. Here we provide an overview of the role of ATRX at chromatin and during development, and discuss recent studies exposing a repertoire of ATRX functions at heterochromatin, in gene regulation, and during mitosis and meiosis. Exciting new progress on several fronts suggest that ATRX operates in histone variant deposition and in the modulation of higher order chromatin structure. Not surprisingly, dysfunction or absence of ATRX protein has devastating consequences on embryonic development and leads to human disease.

scholarly journals CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Martin Franke ◽  
Elisa De la Calle-Mustienes ◽  
Ana Neto ◽  
María Almuedo-Castillo ◽  
Ibai Irastorza-Azcarate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Chromatin Structure ◽  
Zebrafish Model ◽  
Developmental Gene Expression ◽  
Chromatin Interactions ◽  
Fundamental Requirement ◽  
Regulatory Landscapes

AbstractCoordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.

scholarly journals Role of Hfq in iron-dependent and -independent gene regulation in Neisseria meningitidis

Microbiology ◽  
2010 ◽  
Vol 156 (8) ◽  
pp. 2316-2326 ◽  
Author(s):  
J. R. Mellin ◽  
Ryan McClure ◽  
Delia Lopez ◽  
Olivia Green ◽  
Bjorn Reinhard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Neisseria Meningitidis ◽  
Succinate Dehydrogenase ◽  
Transcription Initiation ◽  
Rna Binding ◽  
Intergenic Regions ◽  
Responsive Gene

In Neisseria meningitidis, iron-responsive gene regulation is mediated primarily by the ferric uptake regulator (Fur) protein. When complexed with iron, Fur represses gene expression by preventing transcription initiation. Fur can also indirectly activate gene expression via the repression of regulatory small RNAs (sRNA). One such Fur- and iron-regulated sRNA, NrrF, was previously identified in N. meningitidis and shown to repress expression of the sdhA and sdhC genes encoding subunits of the succinate dehydrogenase complex. In the majority of Gram-negative bacteria, sRNA-mediated regulation requires a cofactor RNA-binding protein (Hfq) for proper gene regulation and stabilization. In this study, we examined the role of Hfq in NrrF-mediated regulation of the succinate dehydrogenase genes in N. meningitidis and the effect of an hfq mutation on iron-responsive gene regulation more broadly. We first demonstrated that the stability of NrrF, as well as the regulation of sdhC and sdhA in vivo, was unaltered in the hfq mutant. Secondly, we established that iron-responsive gene regulation of the Fur-regulated sodB gene was dependent on Hfq. Finally, we demonstrated that in N. meningitidis, Hfq functions in a global manner to control expression of many ORFs and intergenic regions via iron-independent mechanisms. Collectively these studies demonstrate that in N. meningitidis, iron- and NrrF-mediated regulation of sdhC and sdhA can occur independently of Hfq, although Hfq functions more globally to control regulation of other N. meningitidis genes primarily by iron-independent mechanisms.

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

scholarly journals Long Non-Coding RNAs as Endogenous Target Mimics and Exploration of Their Role in Low Nutrient Stress Tolerance in Plants

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 459 ◽  
Author(s):  
Priyanka Borah ◽  
Antara Das ◽  
Matthew Milner ◽  
Arif Ali ◽  
Alison Bentley ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Next Generation Sequencing ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas ◽  
Endogenous Target ◽  
Long Non Coding Rna ◽  
Nutrient Homeostasis ◽  
Generation Sequencing

Long non-coding RNA (lncRNA) research in plants has recently gained momentum taking cues from studies in animals systems. The availability of next-generation sequencing has enabled genome-wide identification of lncRNA in several plant species. Some lncRNAs are inhibitors of microRNA expression and have a function known as target mimicry with the sequestered transcript known as an endogenous target mimic (eTM). The lncRNAs identified to date show diverse mechanisms of gene regulation, most of which remain poorly understood. In this review, we discuss the role of identified putative lncRNAs that may act as eTMs for nutrient-responsive microRNAs (miRNAs) in plants. If functionally validated, these putative lncRNAs would enhance current understanding of the role of lncRNAs in nutrient homeostasis in plants.

Dysregulation of miRNA in cancer progression

2021 ◽  
Author(s):  
Rucha P.
Keyword(s):  
Gene Regulation ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Chromosomal Abnormalities ◽  
Human Cancer ◽  
Epigenetic Modification ◽  
Therapeutic Applications ◽  
Non Coding Rnas ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are a category of highly conserved tiny non-coding RNAs that play a role in post-transcriptional gene regulation. Numerous studies have shown the role of dysregulated miRNA in a variety of illnesses, including human cancer. MiRNA is dysregulated by a variety of processes, including dysregulation of miRNA synthesis, aberrant miRNA transcription, dysregulated epigenetic modification, and chromosomal abnormalities. MiRNAs that are overexpressed have been shown to influence cancer's hallmarks. Recent research has shown miRNA's potential as a therapeutic target and biomarker. In this review, we discussed the synthesis and regulation of miRNA, as well as its dysregulation in human cancer and other disorders, as well as some of the therapeutic applications of miRNA.

scholarly journals OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin An ◽  
Tao Yang ◽  
Jiahao Yang ◽  
Johannes Nuebler ◽  
Guanjue Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Domain Structure ◽  
High Frequency ◽  
Spatial Organization ◽  
Structural Units ◽  
Regulatory Interactions ◽  
Link Type ◽  
Topologically Associating Domains

AbstractThe spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.

The Role of miR-210 in the Biological System: A Current Overview

2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
System A ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
A Current

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

scholarly journals An overview of RNA virus-encoded microRNAs

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Xihan Li ◽  
Xiaoping Zou
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Viral Replication ◽  
Potential Role ◽  
Rna Viruses ◽  
Rna Virus ◽  
Host Cells ◽  
Basic Pattern ◽  
Double Stranded Dna ◽  
Non Coding Rnas

Abstract MicroRNAs (miRNAs) are a number of small non-coding RNAs playing a regulatory part in gene expression. Many virus-encoded miRNAs have been found, which manifests that viruses as well apply the basic pattern of gene regulation, however, mostly in viruses transcribed from double-stranded DNA genomes. It is still in dispute if RNA viruses could encode miRNAs because the excision of miRNA might result in the cleavage of viral RNA genome. We will focus on the miRNAs encoded by RNA virus and discuss their potential role in viral replication cycle and host cells.

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