JMJD5 couples with CDK9 to release the paused RNA polymerase II.

Liu, Haolin; Ramachandran, Srinivas; Fong, Nova; Phang, Tzu; Lee, Schuyler; Parsa, Pirooz; Liu, Xinjian; Harmacek, Laura; Danhorn, Thomas; Song, Tengyao; Oh, Sangphil; Zhang, Qianqian; Chen, Zhongzhou; Zhang, Qian; Tu, Ting-Hui; Happoldt, Carrie; O'Conner, Brian; Janknecht, Ralf; Li, Chuan-Yuan; Marrack, Philippa; Kappler, John; Leach, Sonia; Zhang, Gongyi

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.