Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets

Bruter, Alexandra V.; Rodionova, Mariya D.; Varlamova, Ekaterina A.; Shtil, Alexander А.

doi:10.32607/actanaturae.11067

Cited by 11 publications

(6 citation statements)

References 78 publications

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“…Recently, studies have shown that super-enhancers are capable of regulating a wide swath of genes. These regions contain elevated levels of transcription factors and display characteristics of active chromatin: monomethylation of lysine at position 4 of histone 3 and acetylation of lysine at position 27 of histone 3 [71]. Super-enhancers have been found in genes involved in T-cell activation (IL2RA/CD25, CD30, and FYN) and known cancer genes (TP73, CCR4, TIAM2, NFATC1, NFATC2, and PIK3R1) in ATL cells [72].…”

Section: Discussionmentioning

confidence: 99%

Increased H19/miR-675 Expression in Adult T-Cell Leukemia Is Associated with a Unique Notch Signature Pathway

Bellon,

Nicot

2024

IJMS

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The Notch pathway is a key cancer driver and is important in tumor progression. Early research suggested that Notch activity was highly dependent on the expression of the intracellular cleaved domain of Notch-1 (NICD). However, recent insights into Notch signaling reveal the presence of Notch pathway signatures, which may vary depending on different cancer types and tumor microenvironments. Herein, we perform a comprehensive investigation of the Notch signaling pathway in adult T-cell leukemia (ATL) primary patient samples. Using gene arrays, we demonstrate that the Notch pathway is constitutively activated in ATL patient samples. Furthermore, the activation of Notch in ATL cells remains elevated irrespective of the presence of activating mutations in Notch itself or its repressor, FBXW7, and that ATL cells are dependent upon Notch-1 expression for proliferation and survival. We demonstrate that ATL cells exhibit the expression of pivotal Notch-related genes, including notch-1, hes1, c-myc, H19, and hes4, thereby defining a critical Notch signature associated with ATL disease. Finally, we demonstrate that lncRNA H19 is highly expressed in ATL patient samples and ATL cells and contributes to Notch signaling activation. Collectively, our results shed further light on the Notch pathway in ATL leukemia and reveal new therapeutic approaches to inhibit Notch activation in ATL cells.

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Section: Discussionmentioning

confidence: 99%

Increased H19/miR-675 Expression in Adult T-Cell Leukemia Is Associated with a Unique Notch Signature Pathway

Bellon,

Nicot

2024

IJMS

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“…Nevertheless, there are many other factors which potentially affect SE function and change the transcription probability and rate of dependent genes. For example, it is known that massive eRNA transcription from super-enhancers plays an important role during the cis-regulation of target genes [ 12 ]. At the same time, these eRNAs may modulate the expression of distant genes that are not initially associated with studied super-enhancers.…”

Section: Constitutive Super-enhancers In Different Cell Typesmentioning

confidence: 99%

Experimental Validation and Prediction of Super-Enhancers: Advances and Challenges

Kravchuk

Ashniev

Гладкова

et al. 2023

Cells

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Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and tumorigenesis. Our goal was to systematize research studies dedicated to the investigation of structure and functions of super-enhancers as well as to define further perspectives of the field in various applications, such as drug development and clinical use. We overviewed the fundamental studies which provided experimental data on various pathologies and their associations with particular super-enhancers. The analysis of mainstream approaches for SE search and prediction allowed us to accumulate existing data and propose directions for further algorithmic improvements of SEs’ reliability levels and efficiency. Thus, here we provide the description of the most robust algorithms such as ROSE, imPROSE, and DEEPSEN and suggest their further use for various research and development tasks. The most promising research direction, which is based on topic and number of published studies, are cancer-associated super-enhancers and prospective SE-targeted therapy strategies, most of which are discussed in this review.

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“…Super-enhancers (SE) are described as a cluster of enhancers that have dense assemblies of RNApol II, TFs, and typical enhancer histone modifications (H4K8ac, H3K27ac, and H3K4me) that leads to a greater amount of super-enhancer RNA (seRNA) production ( Figure 2 ) [ 22 ]. The difference between conventional enhancers and SEs is clearly displayed in the nature of the dependence of the transcription activity ensured by the regulatory element and the number of TFs and cofactors associated with it [ 23 ]. The transcription activity at an SE is typically higher than at a distinct enhancer.…”

Section: Biogenesis and Function Of Ernamentioning

confidence: 99%

Emerging Role of Enhancer RNAs as Potential Diagnostic and Prognostic Biomarkers in Cancer

Panahi-Moghadam

Hassani

Farivar

et al. 2022

ncRNA

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Enhancers are distal cis-acting elements that are commonly recognized to regulate gene expression via cooperation with promoters. Along with regulating gene expression, enhancers can be transcribed and generate a class of non-coding RNAs called enhancer RNAs (eRNAs). The current discovery of abundant tissue-specific transcription of enhancers in various diseases such as cancers raises questions about the potential role of eRNAs in disease diagnosis and therapy. This review aimed to demonstrate the current understanding of eRNAs in cancer research with a focus on the potential roles of eRNAs as prognostic and diagnostic biomarkers in cancers.

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Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets

Cited by 11 publications

References 78 publications

Increased H19/miR-675 Expression in Adult T-Cell Leukemia Is Associated with a Unique Notch Signature Pathway

Increased H19/miR-675 Expression in Adult T-Cell Leukemia Is Associated with a Unique Notch Signature Pathway

Experimental Validation and Prediction of Super-Enhancers: Advances and Challenges

Emerging Role of Enhancer RNAs as Potential Diagnostic and Prognostic Biomarkers in Cancer

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