Other
22 Authors
- Liu H,
- Chen Z,
- Happoldt C,
- Song T,
- Zhang Q,
- Janknecht R,
- Zhang G,
- Oh S,
- Kappler J,
- Danhorn T,
- Tu TH,
- Liu X,
- Lee S,
- Marrack P,
- Phang T,
- Parsa P,
- Fong N,
- Harmacek L,
- Li CY,
- Ramachandran S,
- O'Conner B,
- Leach S
| First Author | Liu H | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 33 | Pages | 19888-19895 |
| PubMed ID | 32747552 | Mgi Jnum | J:294185 |
| Mgi Id | MGI:6452006 | Doi | 10.1073/pnas.2005745117 |
| Citation | Liu H, et al. (2020) JMJD5 couples with CDK9 to release the paused RNA polymerase II. Proc Natl Acad Sci U S A 117(33):19888-19895 |
| abstractText | 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. |
