Enhancers play an essential role in gene regulation by receiving cues from transcription factors and relaying these signals to modulate transcription from target promoters. Enhancer-promoter communications occur across large linear distances of the genome and with high specificity. The molecular mechanisms that underlie enhancer-mediated control of transcription remain unresolved. In this review, we focus on research in uncovering the molecular mechanisms governing enhancer-promoter communication and discuss the current understanding of developmental gene regulation. The functions of protein acetylation, pausing of RNA polymerase II, transcriptional bursting, and the formation of nuclear hubs in the induction of tissue-specific programs of transcription during zygotic genome activation are considered.
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http://dx.doi.org/10.1387/ijdb.230218gh | DOI Listing |
bioRxiv
January 2025
Dept. of Biochemistry, University of Colorado, Boulder, CO, 80303, USA.
RNA polymerase II (RNAPII) is regulated by sequence-specific transcription factors (TFs) and the pre-initiation complex (PIC): TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, Mediator. TFs and Mediator contain intrinsically-disordered regions (IDRs) and form phase-separated condensates, but how IDRs control RNAPII function remains poorly understood. Using purified PIC factors, we developed a Real-time In-vitro Fluorescence Transcription assay (RIFT) for second-by-second visualization of RNAPII transcription at hundreds of promoters simultaneously.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Chemistry and Chemical Biology, Center for Quantitative Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA.
The dynamic organization of chromatin plays an essential role in the regulation of genetic activity, interconverting between open and compact forms at the global level. The mechanisms underlying these large-scale changes remain a topic of widespread interest. The simulations of nucleosome-decorated DNA reported herein reveal profound effects of the nucleosome itself on overall chromatin properties.
View Article and Find Full Text PDFSci Adv
December 2024
Division of Gene Expression Dynamics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence-fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors.
View Article and Find Full Text PDFMol Cell
December 2024
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
Curr Opin Genet Dev
November 2024
Department of Developmental and Cell Biology, University of California, Irvine, CA 92967, USA. Electronic address:
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