Transcription

Aryl hydrocarbon receptor (AhR) is a transcription factor that is primarily known as an intracellular sensor of environmental pollution. After five decades, the list of synthetic and toxic chemicals that activate AhR signaling has been extended to include a number of endogenous compounds produced by various types of cells via their metabolic activity. AhR signaling is active from the very beginning of embryonal development throughout the life cycle and participates in numerous biological processes such as control of cell proliferation and differentiation, metabolism of aromatic compounds of endogenous and exogenous origin, tissue regeneration and stratification, immune system development and polarization, control of stemness potential, and homeostasis maintenance...

Bacterial transcription is not monolithic. Microbes exist in a wide variety of cell states that help them adapt to their environment, acquire and produce essential nutrients, and engage in both competition and cooperation with their neighbors. While we typically think of bacterial adaptation as a group behavior, where all cells respond in unison, there is often a mixture of phenotypic responses within a bacterial population, where distinct cell types arise. A primary phenomenon driving these distinct cell states is transcriptional heterogeneity...

No abstract text is available yet for this article.

DNA replication and RNA transcription both utilize DNA as a template and therefore need to coordinate their activities. The predominant theory in the field is that in order for the replication fork to proceed, transcription machinery has to be evicted from DNA until replication is complete. If that does not occur, these machineries collide, and these collisions elicit various repair mechanisms which require displacement of one of the enzymes, often RNA polymerase, in order for replication to proceed. This model is also at the heart of the epigenetic bookmarking theory, which implies that displacement of RNA polymerase during replication requires gradual re-building of chromatin structure, which guides recruitment of transcriptional proteins and resumption of transcription...

RNA polymerases are the central enzymes of gene expression and function frequently in either a head-on or co-directional manner on the busy DNA track. Whether and how these collisions between RNA polymerases contribute to transcriptional regulation is mysterious. Increasing evidence from biochemical and single-molecule studies suggests that RNA polymerase collisions function as an important regulator to fine-tune transcription, rather than creating deleterious "traffic jams". This review summarizes the recent progress on elucidating the consequences of RNA polymerase collisions during transcription and highlights the significance of cooperation and coordination between RNA polymerases...

The development of highly parallel and affordable high-throughput single-cell transcriptomics technologies has revolutionized our understanding of brain complexity. These methods have been used to build cellular maps of the brain, its different regions, and catalog the diversity of cells in each of them during development, aging and even in disease. Now we know that cellular diversity is way beyond what was previously thought. Single-cell transcriptomics analyses have revealed that cell types previously considered homogeneous based on imaging techniques differ depending on several factors including sex, age and location within the brain...

The rising threat of antibiotic resistance in pathogenic bacteria emphasizes the need for new therapeutic strategies. This review focuses on bacterial transcription factors (TFs), which play crucial roles in bacterial pathogenesis. We discuss the regulatory roles of these factors through examples, and we outline potential therapeutic strategies targeting bacterial TFs. Specifically, we discuss the use of small molecules to interfere with TF function and the development of transcription factor decoys, oligonucleotides that compete with promoters for TF binding...

Immune function is highly controlled at the transcriptional level by the binding of transcription factors (TFs) to promoter and enhancer elements. Several TF families play major roles in immune gene expression, including NF-κB, STAT, IRF, AP-1, NRs, and NFAT, which trigger anti-pathogen responses, promote cell differentiation, and maintain immune system homeostasis. Aberrant expression, activation, or sequence of isoforms and variants of these TFs can result in autoimmune and inflammatory diseases as well as hematological and solid tumor cancers...

No abstract text is available yet for this article.

The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts chromatin accessibility, epigenetic marks, and the recruitment of transcriptional regulators. Notably, chromatin is transiently disassembled during S-phase and undergoes drastic condensation during mitosis, which is a significant challenge to the preservation of gene expression patterns between cell generations...

The profiling of gene expression patterns to glean biological insights from single cells has become commonplace over the last few years. However, this approach overlooks the transcript contents that can differ between individual cells and cell populations. In this review, we describe early work in the field of single-cell short-read sequencing as well as full-length isoforms from single cells. We then describe recent work in single-cell long-read sequencing wherein some transcript elements have been observed to work in tandem...

Cell type-specific gene expression is coordinated by DNA-encoded enhancers and the transcription factors (TFs) that bind to them in a sequence-specific manner. As such, these enhancers and TFs are critical mediators of normal development and altered enhancer or TF function is associated with the development of diseases such as cancer. While initially defined by their ability to activate gene transcription in reporter assays, putative enhancer elements are now frequently defined by their unique chromatin features including DNase hypersensitivity and transposase accessibility, bidirectional enhancer RNA (eRNA) transcription, CpG hypomethylation, high H3K27ac and H3K4me1, sequence-specific transcription factor binding, and co-factor recruitment...

RNA polymerase II (Pol II) is composed of 12 subunits that collaborate to synthesize mRNA within the nucleus. Pol II is widely recognized as a passive holoenzyme, with the molecular functions of its subunits largely ignored. Recent studies employing auxin-inducible degron (AID) and multi-omics techniques have revealed that the functional diversity of Pol II is achieved through the differential contributions of its subunits to various transcriptional and post-transcriptional processes. By regulating these processes in a coordinated manner through its subunits, Pol II can optimize its activity for diverse biological functions...

Single-cell sequencing of RNA (scRNA-seq) has advanced our understanding of cellular heterogeneity and signaling in developmental biology and disease. A large number of complementary assays have been developed to profile transcriptomes of individual cells, also in combination with other readouts, such as chromatin accessibility or antibody-based analysis of protein surface markers. As scRNA-seq technologies are advancing fast, it is challenging to establish robust workflows and up-to-date protocols that are best suited to address the large range of research questions...

Across all kingdoms of life, gene regulatory mechanisms underlie cellular adaptation to ever-changing environments. Regulation of gene expression adjusts protein synthesis and, in turn, cellular growth. Messenger RNAs are key molecules in the process of gene expression. Our ability to quantitatively measure mRNA expression in single cells has improved tremendously over the past decades. This revealed an unexpected coordination between the steps that control the life of an mRNA, from transcription to degradation...

Caenorhabditis elegans can enter a diapause stage called "dauer" when it senses that the environment is not suitable for development. This implies a detour from the typical developmental trajectory and requires a tight control of the developmental clock and a massive tissue remodeling. In the last decades, core components of the signaling pathways that govern the dauer development decision have been identified, but the tissues where they function for the acquisition of dauer-specific traits are still under intense study...

Proximity ligation assay (PLA) is an immunofluorescence assay, which determines in situ interaction of two biomolecules present within 40 nm close proximity. Here, we describe a modification of PLA for visual detection of in situ protein interactions with nascent RNA in a single cell (IPNR-PLA). In IPNR-PLA, nascent RNA is labeled by incorporating 5-fluorouridine (FU), a uridine nucleotide analogue, followed by covalent cross-linking of the interacting partners in proximity to newly synthesized RNA. By using combination of anti-BrdU antibody, which specifically binds to FU, and primary antibody against a protein of interest, the IPNR reaction results in fluorescent puncta as a positive signal, only if the candidate proteins are in proximity to nascent RNA...

Eukaryotic cells rely upon dynamic, multifaceted regulation at each step of RNA biogenesis to maintain mRNA pools and ensure normal protein synthesis. Studies in budding yeast indicate a buffering phenomenon that preserves global mRNA levels through the reciprocal balancing of RNA synthesis rates and mRNA decay. In short, changes in transcription impact the efficiency of mRNA degradation and defects in either nuclear or cytoplasmic mRNA degradation are somehow sensed and relayed to control a compensatory change in mRNA transcription rates...

Microsporidia are eukaryotic obligate intracellular parasites closely related to fungi. Co-evolving with infected hosts, microsporidia have highly reduced their genomes and lacked several biological components. As it is beneficial for intracellular parasites like microsporidia to reduce their genome size, it is therefore reasonable to assume that genes encoding multifactorial complex machinery of transcription could be a potential target to be excluded from microsporidian genomes during the reductive evolution...

Transcription termination is known to occur via two mechanisms in bacteria, intrinsic termination (also frequently referred to as Rho-independent or factor-independent termination) and Rho-dependent termination. Based primarily on in vitro studies using Escherichia coli RNA polymerase, it was generally assumed that intrinsic termination and Rho-dependent termination are distinct mechanisms and that the signals required for intrinsic termination are present primarily within the nucleic acids. In this review, we detail recent findings from studies in Bacillus subtilis showing that intrinsic termination in this organism is highly stimulated by NusA, NusG, and even Rho...