Molecular Basis of the Function of Transcriptional Enhancers

Ibragimov, A. N.; Bylino, Oleg V.; Shidlovskii, Yulii V.

doi:10.3390/cells9071620

Cited by 11 publications

(10 citation statements)

References 216 publications

(352 reference statements)

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“…The system described here has allowed us to reveal novel aspects of the role that the remodeler plays in enhancer-dependent transcription, thus extending our knowledge about molecular mechanisms of enhancer action [ 74 , 75 ]. Moreover, recent data point to a localization of the remodeler on chromatin boundaries and its role in the formation of the global chromatin structure [ 15 , 76 , 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in Drosophila

Shidlovskii

Bylino

Шапошников

et al. 2021

IJMS

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The chromatin remodeler SWI/SNF is an important participant in gene activation, functioning predominantly by opening the chromatin structure on promoters and enhancers. Here, we describe its novel mode of action in which SWI/SNF factors mediate the targeted action of an enhancer. We studied the functions of two signature subunits of PBAP subfamily, BAP170 and SAYP, in Drosophila. These subunits were stably tethered to a transgene reporter carrying the hsp70 core promoter. The tethered subunits mediate transcription of the reporter in a pattern that is generated by enhancers close to the insertion site in multiple loci throughout the genome. Both tethered SAYP and BAP170 recruit the whole PBAP complex to the reporter promoter. However, we found that BAP170-dependent transcription is more resistant to the depletion of other PBAP subunits, suggesting that BAP170 may play a more critical role in establishing enhancer-dependent transcription.

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Section: Discussionmentioning

confidence: 99%

Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in Drosophila

Shidlovskii

Bylino

Шапошников

et al. 2021

IJMS

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“…However, although the mechanisms of transcriptional control drastically differ between Metazoa and Bacteria, it is still possible to observe the original prototypes of complex eukaryotic mechanisms in Bacteria. Our current understanding of these mechanisms is far from complete [ 194 ]. Further studies are necessary because comprehensive knowledge of the function of these genomic elements is highly important for multiple applications in biotechnological and medical fields [ 272 , 273 ].…”

Section: Discussionmentioning

confidence: 99%

“…To overcome redundancy and to induce a high level of target gene transcription, activators should act in combination with each other, binding multiple regulatory elements in enhancers. In addition, they should act in a proper chromatin context (chromatin context requirements are reviewed in [ 194 ]). This combinatorial code is additionally reflected in the fact that, compared with prokaryotic TFs, eukaryotic TFs are often heterodimeric in structure, each of the monomers recognizing a similar, but slightly different sequence.…”

Section: Mechanisms Of Transcription Activation In Eukaryotesmentioning

confidence: 99%

“…Although small loops are more likely to form than large loops at first glance, this model is doubtful currently, after the discovery of the loop extrusion mechanism functioning in vivo. ncRNAs produced by RNAP are found between the enhancer(s) and promoter (for details, see [ 194 ]). The ncRNAs directed towards the promoter may reflect the process whereby RNAP seeks for stable binding to a promoter [ 221 ].…”

Section: Current Models Of Enhancer Functioning In Eukaryotesmentioning

confidence: 99%

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Evolution of Regulated Transcription

Bylino

Ibragimov

Shidlovskii

2020

Cells

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The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual evolution of this regulatory system and discuss its features in different organisms. In eubacteria, an enhancer-like element is often a single regulatory element, is usually proximal to the core promoter, and is occupied by one or a few activators. Activation of gene expression in archaea is accompanied by the recruitment of an activator to several enhancer-like sites in the upstream promoter region. In eukaryotes, activation of expression is accompanied by the recruitment of activators to multiple enhancers, which may be distant from the core promoter, and the activators act through coactivators. The role of the general DNA architecture in transcription control increases in evolution. As a whole, it can be seen that enhancers of multicellular eukaryotes evolved from the corresponding prototypic enhancer-like regulatory elements with the gradually increasing genome size of organisms.

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“…The primary difference is their location, as they can be found up to 1 Mb upstream or downstream from their target gene, or even within introns of nearby genes [ 7 , 8 ]. Enhancer elements serve as docking platforms enriched in specific TF binding sites, where the binding of pioneering TF can recruit additional co-activator proteins, including the histone deacetylases p300/CBP, large multi-protein complexes such as Mediator, or even cell type- and lineage-specific co-activators crucial to determining cell fate ( Figure 1 ) [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Genome Organization in Breast and Gynecological Cancers: How Chromatin Folding Influences Tumorigenic Transcriptional Programs

Nuñez‐Olvera

Puente-Rivera

Ramos‐Payán

et al. 2021

Cells

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A growing body of research on the transcriptome and cancer genome has demonstrated that many gynecological tumor-specific gene mutations are located in cis-regulatory elements. Through chromosomal looping, cis-regulatory elements interact which each other to control gene expression by bringing distant regulatory elements, such as enhancers and insulators, into close proximity with promoters. It is well known that chromatin connections may be disrupted in cancer cells, promoting transcriptional dysregulation and the expression of abnormal tumor suppressor genes and oncogenes. In this review, we examine the roles of alterations in 3D chromatin interactions. This includes changes in CTCF protein function, cancer-risk single nucleotide polymorphisms, viral integration, and hormonal response as part of the mechanisms that lead to the acquisition of enhancers or super-enhancers. The translocation of existing enhancers, as well as enhancer loss or acquisition of insulator elements that interact with gene promoters, is also revised. Remarkably, similar processes that modify 3D chromatin contacts in gene promoters may also influence the expression of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which have emerged as key regulators of gene expression in a variety of cancers, including gynecological malignancies.

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Molecular Basis of the Function of Transcriptional Enhancers

Cited by 11 publications

References 216 publications

Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in Drosophila

Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in Drosophila

Evolution of Regulated Transcription

Three-Dimensional Genome Organization in Breast and Gynecological Cancers: How Chromatin Folding Influences Tumorigenic Transcriptional Programs

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