Core promoter activity contributes to chromatin-based regulation of internal cryptic promoters
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Lee, Bo Bae; Woo, Hyeonju; Lee, Min Kyung; Youn, SeoJung; Lee, Sumin; Lee, Soo Young; Kim, TaeSoo] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Lee, Bo Bae; Woo, Hyeonju; Lee, Min Kyung; Youn, SeoJung; Lee, Sumin; Lee, Soo Young; Kim, TaeSoo] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea; [Roe, Jae-Seok] Yonsei Univ, Dept Biochem, Coll Life Sci & Biotechnol, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 OXFORD UNIV PRESS
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183512
- 본문언어 영어
- Published As http://dx.doi.org/10.1093/nar/gkab639
- PubMed https://pubmed.ncbi.nlm.nih.gov/34320189
초록/요약
During RNA polymerase II (RNA Pol II) transcription, the chromatin structure undergoes dynamic changes, including opening and closing of the nucleosome to enhance transcription elongation and fidelity. These changes are mediated by transcription elongation factors, including Spt6, the FACT complex, and the Set2-Rpd3S HDAC pathway. These factors not only contribute to RNA Pol II elongation, reset the repressive chromatin structures after RNA Pol II has passed, thereby inhibiting aberrant transcription initiation from the internal cryptic promoters within gene bodies. Notably, the internal cryptic promoters of infrequently transcribed genes are sensitive to such chromatin-based regulation but those of hyperactive genes are not. To determine why, the weak core promoters of genes that generate cryptic transcripts in cells lacking transcription elongation factors (e.g. STE11) were replaced with those from more active genes. Interestingly, as core promoter activity increased, activation of internal cryptic promoter dropped. This associated with loss of active histone modifications at the internal cryptic promoter. Moreover, environmental changes and transcription elongation factor mutations that downregulated the core promoters of highly active genes concomitantly increased their cryptic transcription. We therefore propose that the chromatin-based regulation of internal cryptic promoters is mediated by core promoter strength as well as transcription elongation factors.
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