JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity[2]. Knockouts of JMJD5 and JMJD7 dramatically increase the content of arginine-methylated histone tails as well as the overall content of histone subunits in cells. Deletion of JMJD7 genes in human breast cancer cells drastically reduces their growth in soft agar[3]. JMJD7 was present at gene promoters and its promoter occupancy changed upon osteoclast differentiation. Further, JMJD7 downregulation caused more rapid osteoclast differentiation[4]. The JMJD7-PLA2G4B fusion protein does not encompass the full JmjC domain of JMJD7-predicting absence of any enzymatic activity - but consists of nearly the whole PLA2G4B protein, the functions of JMJD7-PLA2G4B are likely to match those of PLA2G4B. In the same vein, the association of a sequence variant of the JMJD7-PLA2G4B gene with high-risk autism is unlikely due to dysregulated JMJD7 enzymatic activity[5]. JMJD7-IN-1 efficiently binds to JMJD7, with an IC50 of 3.80 μM. JMJD7-IN-1 (72 h) inhibits the growth of T-47d, SK-BR-3, Jurkat and Hela cells, with IC50s of 9.40 μM, 13.26 μM, 15.03 μM and 16.14 μM, respectively. JMJD7-IN-1 (0.1-1000 μM) dose-dependently inhibits the activity of JMJD7, with an IC50 of 6.62 μM[6].
搜索
