Transcription-Austin最新文献

Enhancers are defined as regulatory elements that control transcription in a cell-type and developmental stage-specific manner. They achieve this by physically interacting with their cognate gene promoters. Significantly, these interactions can occur through long genomic distances since enhancers may not be near their cognate promoters. The optimal coordination of enhancer-regulated transcription is essential for the function and identity of the cell. Although great efforts to fully understand the principles of this type of regulation are ongoing, other potential functions of the long-range chromatin interactions (LRCIs) involving enhancers are largely unexplored. We recently uncovered a new role for enhancer elements in determining the three-dimensional (3D) structure of the immunoglobulin kappa (Igκ) light chain receptor locus suggesting a structural function for these DNA elements. This enhancer-mediated locus configuration shapes the resulting Igκ repertoire. We also propose a role for enhancers as critical components of sub-topologically associating domain (subTAD) formation and nuclear spatial localization.

Enhancers are cis-acting elements with many sites bound by transcription factors and activate transcription over long distance. Histone modifications are critical for enhancer activity and utilized as hallmarks for the identification of putative enhancers. Monomethylation of histone H3 lysine 4 (H3K4me1) is the mark for enhancer priming; acetylation of histone H3 lysine 27 (H3K27ac) for active enhancers and trimethylation of histone H3 lysine 27 (H3K27me3) for silent enhancers. Recent studies from multiple groups have provided evidence that enhancer reprogramming, especially gain of enhancer activity, is closely related to tumorigenesis and cancer development. In this review, we will summarize the recent discoveries about enhancer regulation and the mechanisms of enhancer reprogramming in tumorigenesis, and discuss the potential application of enhancer manipulation in precision medicine.

Bacteriophages employ small proteins to usurp host molecular machinery, thereby interfering with central metabolic processes in infected bacteria. Generally, phages inhibit or redirect host transcription to favor transcription of their own genomes. Mechanistic and structural studies of phage-modulated host transcription may provide inspirations for the development of novel antibacterial substances.

Gene transcription is regulated with distinct sets of regulatory factors at multiple levels. Transcriptional and post-transcriptional regulation constitute two major regulation modes of gene expression to either activate or repress the initiation of transcription and thereby control the number of proteins synthesized during translation. Disruptions of the proper regulation patterns at transcriptional and post-transcriptional levels are increasingly recognized as causes of human diseases. Consequently, identifying the differential gene expression at transcriptional and post-transcriptional levels respectively is vital to identify potential disease-associated and/or causal genes and understand their roles in the disease development. Here, we proposed a novel method with a linear mixed model that can identify a set of differentially expressed genes at transcriptional and post-transcriptional levels. The simulation and real data analysis showed our method could provide an accurate way to identify genes subject to aberrant transcriptional and post-transcriptional regulation and reveal the potential causal genes that contributed to the diseases.

We recently reported that the cyclin T1 histidine-rich domain creates a phase-separated environment to promote hyperphosphorylation of RNA polymerase II C-terminal domain and robust transcriptional elongation by P-TEFb. Here, we discuss this and several other recent discoveries to demonstrate that phase separation is important for controlling various aspects of transcription.