Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements.

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.

Structural biology has a strong interest in ion channels, a diverse group of membrane proteins. This group has long remained difficult to study, but much progress has been made in recent decades with improvements in biochemical methods and computational procedures. Voltage-gated ion channels undergo conformational changes upon functioning, and multiple models of activation mechanisms were proposed based on experimental data. This review focuses on the structural studies of the functioning of voltage-gated ion channels, which are accompanied by conformational changes in proteins, and the methodological advances that allow their observation. Modern experimental methods that allow obtaining ion channel proteins in specific functional states are discussed, including cryoelectron microscopy and cryoelectron tomography. Finally, new algorithms for studying the conformational mobility of proteins have been developed, which help to better understand the mechanisms of ion channel domain movements.