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Structural insight into nucleosome transcription by RNA polymerase II with elongation factors

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Science  15 Feb 2019:
Vol. 363, Issue 6428, pp. 744-747
DOI: 10.1126/science.aav8912

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Getting over nucleosomal barriers

In eukaryotic cells, RNA polymerase II (RNAPII) transcribes DNA within nucleosome-coated chromatin. The nucleosomes can provide major roadblocks for transcription. Cells solve this problem by using transcription elongation factors. Ehara et al. solved the cryo–electron microscopy structures of the nucleosome-transcribing RNAPII with elongation factors Elf1 and Spt4/5. Elf1 and Spt4/5 cooperatively suppress RNAPII pausing at multiple super helical locations [SHL(−6), SHL(−5), and SHL(−2)] and facilitate RNAPII progression through SHL(−1) by adjusting the nucleosome position to favor forward progression.

Science, this issue p. 744

Abstract

RNA polymerase II (RNAPII) transcribes chromosomal DNA that contains multiple nucleosomes. The nucleosome forms transcriptional barriers, and nucleosomal transcription requires several additional factors in vivo. We demonstrate that the transcription elongation factors Elf1 and Spt4/5 cooperatively lower the barriers and increase the RNAPII processivity in the nucleosome. The cryo–electron microscopy structures of the nucleosome-transcribing RNAPII elongation complexes (ECs) reveal that Elf1 and Spt4/5 reshape the EC downstream edge and intervene between RNAPII and the nucleosome. They facilitate RNAPII progression through superhelical location SHL(–1) by adjusting the nucleosome in favor of the forward progression. They suppress pausing at SHL(–5) by preventing the stable RNAPII-nucleosome interaction. Thus, the EC overcomes the nucleosomal barriers while providing a platform for various chromatin functions.

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