Structural basis of nucleosome retention during transcription elongation


Martin Filipovski, Jelly H. M. Soffers, Seychelle M. Vos, and Lucas Farnung. 6/16/2022. “Structural basis of nucleosome retention during transcription elongation.” Science, 376, 6599, Pp. 1313-1316. Publisher's Version


In eukaryotes, RNA polymerase (Pol) II transcribes chromatin and must move past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes has been unclear. Here, we report the 3.0-angstrom cryo–electron microscopy structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex stalled 54 base pairs within the nucleosome. The structure provides a mechanistic basis for nucleosome retention during transcription elongation where upstream DNA emerging from the Pol II cleft has rewrapped the proximal side of the nucleosome. The structure uncovers a direct role for Pol II and transcription elongation factors in nucleosome retention and explains how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes. Eukaryotic cells organize their large genomes into a compacted structure called chromatin. The condensed structure of chromatin, with its fundamental unit the nucleosome, represents a challenge to nucleic acid–transacting machines including RNA polymerase II (Pol II), the enzyme responsible for the transcription of most protein-coding genes. How RNA Pol II overcomes nucleosomes without disrupting chromatin organization remains unknown. Using cryo–electron microscopy, Filipovski et al. provided structural snapshots of a complex between mammalian RNA Pol II and a nucleosome that show how previously transcribed DNA rewraps the nucleosome. The finding provides a structural basis of how nucleosomes, and consequently epigenetic marks, are retained during transcription. —DJ A high-resolution cryo–electron microscopy structure explains how nucleosomes are retained to prevent disruption of chromatin across actively transcribed genes.
Last updated on 06/16/2022