Farnung Lucas
Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
J Mol Biol. 2025 Jan 1;437(1):168845. doi: 10.1016/j.jmb.2024.168845. Epub 2024 Oct 29.
In eukaryotic cells, transcription by RNA polymerase II occurs in the context of chromatin, requiring the transcription machinery to navigate through nucleosomes as it traverses gene bodies. Recent advances in structural biology have provided unprecedented insights into the mechanisms underlying transcription elongation. This review presents a structural perspective on transcription through chromatin, focusing on the latest findings from high-resolution structures of transcribing RNA polymerase II-nucleosome complexes. I discuss how RNA polymerase II, in concert with elongation factors such as SPT4/5, SPT6, ELOF1, and the PAF1 complex, engages with and transcribes through nucleosomes. The review examines the stepwise unwrapping of nucleosomal DNA as polymerase advances, the roles of elongation factors in facilitating this process, and the mechanisms of nucleosome retention and transfer during transcription. This structural perspective provides a foundation for understanding the intricate interplay between the transcription machinery and chromatin, offering insights into how cells balance the need for genetic accessibility with the maintenance of genome stability and epigenetic regulation.
在真核细胞中,RNA聚合酶II的转录发生在染色质环境中,这要求转录机制在穿越基因体时穿过核小体。结构生物学的最新进展为转录延伸的潜在机制提供了前所未有的见解。本综述从结构角度阐述了通过染色质的转录,重点关注转录RNA聚合酶II-核小体复合物高分辨率结构的最新发现。我将讨论RNA聚合酶II如何与SPT4/5、SPT6、ELOF1和PAF1复合物等延伸因子协同作用,与核小体结合并进行转录。本综述研究了随着聚合酶前进核小体DNA的逐步解旋、延伸因子在促进这一过程中的作用,以及转录过程中核小体保留和转移的机制。这种结构观点为理解转录机制与染色质之间的复杂相互作用提供了基础,有助于深入了解细胞如何在遗传可及性需求与基因组稳定性和表观遗传调控的维持之间取得平衡。