β-Globin Intergenic Transcription and Histone Acetylation Dependent on an Enhancer

Kim, AeRi; Zhao, Hui; Ifrim, Ina; Dean, Ann

doi:10.1128/mcb.02337-06

Cited by 41 publications

(40 citation statements)

References 51 publications

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“…We note that while this trend holds true globally, intergenic elements have a continuum of directionality, with some (putative) enhancers displaying bidirectional transcription that is asymmetrically biased to one strand or unidirectional transcription (44% of intergenic elements have an OI > 0.8). This property is also observed in mammals (Ho et al 2006;Kim et al 2007;De Santa et al 2010;Koch et al 2011) and is one that we explore in more detail below.…”

Section: Resultsmentioning

confidence: 63%

“…Mammalian eRNAs are generally nonpolyadenlyated, low in abundance, unspliced, and retained within the nucleus (De Santa et al 2010;Kim et al 2010;Core et al 2012;Andersson et al 2014a,b). They are often bidirectionally transcribed (Kim et al 2010;Melgar et al 2011;Hah et al 2013;Kaikkonen et al 2013;Andersson et al 2014a), although some unidirectional transcription has also been reported (Ho et al 2006;Kim et al 2007;De Santa et al 2010;Koch et al 2011). In Caenorhabditis elegans, putative enhancers (intergenic TF-bound regions) have bidirectional eRNA transcription but form longer transcripts in the direction of the closest downstream gene (Chen et al 2013).…”

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confidence: 99%

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The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

et al. 2018

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Gene expression is regulated by promoters, which initiate transcription, and enhancers, which control their temporal and spatial activity. However, the discovery that mammalian enhancers also initiate transcription questions the inherent differences between enhancers and promoters. Here, we investigate the transcriptional properties of enhancers during Drosophila embryogenesis using characterized developmental enhancers. We show that while the timing of enhancer transcription is generally correlated with enhancer activity, the levels and directionality of transcription are highly varied among active enhancers. To assess how this impacts function, we developed a dual transgenic assay to simultaneously measure enhancer and promoter activities from a single element in the same embryo. Extensive transgenic analysis revealed a relationship between the direction of endogenous transcription and the ability to function as an enhancer or promoter in vivo, although enhancer RNA (eRNA) production and activity are not always strictly coupled. Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio-temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot. The balance between enhancer and promoter activity is generally reflected in the levels and directionality of eRNA transcription and is likely an inherent sequence property of the elements themselves.

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Section: Resultsmentioning

confidence: 63%

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confidence: 99%

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

et al. 2018

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“…2E). [77][78][79] Contraction of decondensed chromatin due to "depletion attraction forces" could also contributes to the loop formation. 80 In favor of this idea, it was shown that formation of a chromatin loop topologically isolating the enhancer from the target promoter is sufficient to inhibit enhancer's activity in vivo.…”

Section: Dna Topology and Genome Architecturementioning

confidence: 99%

DNA topology and transcription

Kouzine¹,

Levens²,

Baranello³

2014

Nucleus

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Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.

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“…They play an important role in imprinting (7), enhancing various biological functions (8), X chromosome inactivation (9), chromatin structure (10) and genomic rearrangement during the generation of antibody diversity (11). Thus, lncRNAs are critical for normal development and, in many cases, are deregulated in diseases, such as cancer (12).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

Cao

Zhang

Wang

et al. 2013

International Journal of Molecular Medicine

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Abstract. Recent studies suggest that long non-coding RNAs (lncRNAs) are more involved in human diseases than previously realized. A growing body of evidence links lncRNA mutation and dysregulation to diverse human diseases. However, the association of lncRNAs with the pathogenesis of lung fibrosis remains poorly understood. In this study, we detected changes in hydroxyproline and collagen levels, as well as the ultrastructure of lung tissue to develop a rat model of lung fibrosis. The differentially expressed lncRNAs and mRNA profiles between fibrotic lung and normal lung tissue were analyzed using microarrays. Gene Ontology analysis and pathway analysis were performed for further research. Two differentially expressed lncRNAs, namely, AJ005396 and S69206, were detected by in situ hybridization to validate the microarray data. The results revealed that the number of collagen fibers in the interstitial lung tissue significantly increased in the model group compared with the normal group. In total, 210 and 358 lncRNAs were upregulated and downregulated, respectively, along with 415 upregulated and 530 downregulated mRNAs in the rats with lung fibrosis. AJ005396 and S69206 were upregulated in the fibrotic lung tissue, consistent with the microarray data, and were located in the cytoplasm of the interstitial lung cells. In conclusion, the expression profile of the lncRNAs was significantly altered in the fibrotic lung tissue and these transcripts are potential molecular targets for inhibiting the development of lung fibrosis. IntroductionIdiopathic pulmonary fibrosis (IPF) is a common, chronic, progressive and usually lethal fibrotic lung disease with poor prognosis (1). This disease is characterized by focal areas of alveolar epithelial cell injury and the excessive proliferation of mesenchymal cells in the interstitium, which results in the excessive deposition of extracellular matrix (ECM) and distorted architecture leading to impaired gas exchange (2,3). Although many pathobiological concepts are emerging, including the role of aging and cellular senescence, oxidative stress, endoplasmic reticulum stress, cellular plasticity, microRNA (miRNA) and mechanotransduction, the molecular mechanisms behind IPF are not yet completely understood (4).The Encyclopedia of DNA Elements (ENCODE) project, which aimed to comprehensively characterize the human genome, has shown that >90% of the genome has been transcribed; however, only 1-2% of that is composed of genes (5). The majority of these transcripts are not translated into proteins and are, therefore, termed non-coding RNAs (ncRNAs).Long non-coding RNAs (lncRNAs), a type of ncRNA, vary in size from 200 bp to >100 kb, and are transcribed by RNA polymerase II (6). They play an important role in imprinting (7), enhancing various biological functions (8), X chromosome inactivation (9), chromatin structure (10) and genomic rearrangement during the generation of antibody diversity (11). Thus, lncRNAs are critical for normal development and, in many cases, are deregulated in d...

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β-Globin Intergenic Transcription and Histone Acetylation Dependent on an Enhancer

Cited by 41 publications

References 51 publications

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

DNA topology and transcription

Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

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