Transcription-Austin最新文献

Genome compaction is a common evolutionary feature of parasites. The unicellular, obligate intracellular parasite Encephalitozoon cuniculi has one of smallest known eukaryotic genomes, and is nearly four times smaller than its distant fungi relative, the budding yeast Saccharomyces cerevisiae. Comparison of the proteins encoded by compacted genomes to those encoded by larger genomes can reveal the most highly conserved features of the encoded proteins. In this study, we identified the proteins comprising the RNA polymerases and their corresponding general transcription factors by using several bioinformatic approaches to compare the transcription machinery of E. cuniculi and S. cerevisiae. Surprisingly, our analyses revealed an overall reduction in the size of the proteins comprising transcription machinery of E. cuniculi, which includes the loss of entire regions or functional domains from proteins, as well as the loss of entire proteins and complexes. Unexpectedly, we found that the E. cuniculi ortholog of Rpc37 (a RNA Polymerase III subunit) more closely resembles the H. sapiens ortholog of Rpc37 than the S. cerevisiae ortholog of Rpc37, in both size and structure. Overall, our findings provide new insight into the minimal core eukaryotic transcription machinery and help define the most critical features of Pol components and general transcription factors.

Low-dimensional negative feedback systems (NFSs) were developed within a signal flow model to describe the oscillatory activities of NF-κB caused by interactions with its inhibitor IκBα. The NFSs were established as 3^rd- and 4^th-order linear systems containing unperturbed and perturbed negative feedback (NF) loops with constant or time-varying NF strengths and a feed-forward loop. NF-related analytical solutions to the NFSs representing the time courses of NF-κB and IκBα were determined and their exact mathematical relationship was found. The NFS's parameters were determined to fit the experimental time courses of NF-κB in TNF-α-stimulated embryonic fibroblasts, rela^-/- embryonic fibroblasts reconstituted with RelA, C9L cells, GFP-p65 knock-in embryonic fibroblasts and embryogenic fibroblasts lacking Iκβ and IκBε, LPS-stimulated IC-21 macrophages treated or not with DCPA, and anti-IgM-stimulated DT40 B-lymphocytes. The unperturbed and perturbed NFSs describing the above biosystems generated isochronous and non-isochronous solutions, depending on a constant or time-varying NF strength, respectively. The oscillation period of the NF-coupled solutions, the phase difference between them and the time delays in the appearance of cytoplasmic IκBα after stimulation of NF-κB were determined. A significant divergence between the IκBα solutions to the NFSs and the IκBα experimental courses led to a rejection of the NF coupling between NF-κB and IκBα in the above biosystems. It was shown that neither the linearity nor the low dimensionality of the NFSs altered the NF relationship and the divergence between the IκBα solutions to the NFS and IκBα experimental time courses. Although the NF relationship between IκBα and NF-κB was not confirmed in all the experimental data analyzed, delayed negative feedback was found in some cases.

Transcription factors (TFs) intricately navigate the vast genomic landscape to locate and bind specific DNA sequences for the regulation of gene expression programs. These interactions occur within a dynamic cellular environment, where both DNA and TF proteins experience continual chemical and structural perturbations, including epigenetic modifications, DNA damage, mechanical stress, and post-translational modifications (PTMs). While many of these factors impact TF-DNA binding interactions, understanding their effects remains challenging and incomplete. This review explores the existing literature on these dynamic changes and their potential impact on TF-DNA interactions.

The SorC family is a large group of bacterial transcription regulators involved in controlling carbohydrate catabolism and quorum sensing. SorC proteins consist of a conserved C-terminal effector-binding domain and an N-terminal DNA-binding domain, whose type divides the family into two subfamilies: SorC/DeoR and SorC/CggR. Proteins of the SorC/CggR subfamily are known to regulate the key node of glycolysis-triose phosphate interconversion. On the other hand, SorC/DeoR proteins are involved in a variety of peripheral carbohydrate catabolic pathways and quorum sensing functions, including virulence. Despite the abundance and importance of this family, SorC proteins seem to be on the periphery of scientific interest, which might be caused by the fragmentary information about its representatives. This review aims to compile the existing knowledge and provide material to inspire future questions about the SorC protein family.

Genotoxic stress resulting from DNA damage is resolved through a signaling cascade known as the DNA Damage Response (DDR). The repair of damaged DNA is essential for cell survival, often requiring the DDR to attenuate other cellular processes such as the cell cycle, DNA replication, and transcription of genes not involved in DDR. The complex relationship between DDR and transcription has only recently been investigated. Transcription can facilitate the DDR in response to double-strand breaks (DSBs) and stimulate nucleotide excision repair (NER). However, transcription may need to be reduced to prevent potential interference with the repair machinery. In this review, we discuss various mechanisms that regulate transcription repression in response to different types of DNA damage, categorizing them by their range and duration of effect. Finally, we explore various models of transcription recovery following DNA damage-induced repression.

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.

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. Given that bacterial mRNA transcripts are extremely short-lived compared to eukaryotes, their transcriptional state is closely associated with their physiology, and thus the transcriptome of a bacterial cell acts as a snapshot of the behavior of that bacterium. Therefore, the application of single-cell transcriptomics to microbial populations will provide novel insight into cellular differentiation and bacterial ecology. In this review, we provide an overview of transcriptional heterogeneity in microbial systems, discuss the findings already provided by single-cell approaches, and plot new avenues of inquiry in transcriptional regulation, cellular biology, and mechanisms of heterogeneity that are made possible when microbial communities are analyzed at single-cell resolution.

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. We discuss these theories but also bring to light newer data that suggest that these two processes may not be as detrimental to one another as previously thought. This includes findings suggesting that these processes can occur without fork collapse and that RNA polymerase may only be transiently displaced during DNA replication. We discuss potential mechanisms by which RNA polymerase may be retained at the replication fork and quickly rebind to DNA post-replication. These discoveries are important, not only as new evidence as to how these two processes are able to occur harmoniously but also because they have implications on how transcriptional programs are maintained through DNA replication. To this end, we also discuss the coordination of replication and transcription in light of revising the current epigenetic bookmarking theory of how the active gene status can be transmitted through S phase.

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. This article delves into the specific gene expression and chromatin regulatory mechanisms that facilitate the preservation of transcriptional identity during replication and mitosis. Furthermore, we emphasize our recent findings revealing the unconventional role of yeast centromeres and mitotic chromosomes in maintaining transcriptional fidelity beyond mitosis.