JMJD5 couples with CDK9 to release the paused RNA polymerase II.
Proc Natl Acad Sci U S A
; 117(33): 19888-19895, 2020 08 18.
Article
en En
| MEDLINE
| ID: mdl-32747552
ABSTRACT
More than 30% of genes in higher eukaryotes are regulated by RNA polymerase II (Pol II) promoter proximal pausing. Pausing is released by the positive transcription elongation factor complex (P-TEFb). However, the exact mechanism by which this occurs and whether phosphorylation of the carboxyl-terminal domain of Pol II is involved in the process remains unknown. We previously reported that JMJD5 could generate tailless nucleosomes at position +1 from transcription start sites (TSS), thus perhaps enable progression of Pol II. Here we find that knockout of JMJD5 leads to accumulation of nucleosomes at position +1. Absence of JMJD5 also results in loss of or lowered transcription of a large number of genes. Interestingly, we found that phosphorylation, by CDK9, of Ser2 within two neighboring heptad repeats in the carboxyl-terminal domain of Pol II, together with phosphorylation of Ser5 within the second repeat, HR-Ser2p (1, 2)-Ser5p (2) for short, allows Pol II to bind JMJD5 via engagement of the N-terminal domain of JMJD5. We suggest that these events bring JMJD5 near the nucleosome at position +1, thus allowing JMJD5 to clip histones on this nucleosome, a phenomenon that may contribute to release of Pol II pausing.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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ARN Polimerasa II
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Quinasa 9 Dependiente de la Ciclina
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Histona Demetilasas
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article