pause enhancer. This process was linked to the promoter proximal pause release of a large group of transcription units. The release from pol II pause release is mainly down to the function of P-TEFb complex which is known to phosphorylate three targets. In cells at ~50% of the P-TEFb complex is bound to the inhibitory factor HEXIM1/2 and 7sk snRNA the other ~50% is bound to Brd4. Brd4 is able to directly release P-TEFb from the inhibitory factors (HEXIM1/2 and 7sk snRNA) via interactions with cyclin T1 which results in the P-TEFb becoming active and the phosphorylation of RNA pol II and therefore starting transcription. Jmjd6 was found to work with Brd4 as a partner in the regulation of transcription for a large subset of genes. This regulation was observed to be via their interactions with distal enhancers called anti-pause enhancers (A-PE’s). Jmjd6 was found to display demethylase activities towards the H4R3me2(s) and the 7SK snRNA cap resulting in the release of the inhibitory complex called 7SK snRNA/HEXIM. (maybe use section from initial review to discuss) (reference)

Histone arginine demethylation-

Early in the 1960s it was first observed that histones undergo post translational modification and in 1997 using the high resolution x-ray images of the nucleosomes were used to hypothesise the effect of histone modification on chromatin structure. It was observed that histone n-terminal tails can stick out from the nucleosome and touch other nearby nucleosomes. The interactions between nucleosomes were then thought to be able to be modified by post translational modifications such as demethylation. It is now known that this is true and post translational modification of histones have been displayed to play roles in recruitment of enzymes such as remodelling enzymes which remove histones using energy attained from ATP hydrolysis. There are two main mechanisms that histone modifications produce effects. The first of these is the post translational modification resulting in an alteration of the structure of chromatin. The second is the modification resulting in the positive or negative regulation of effector molecule binding. These modifications have been found to be important in transcription as well as DNA replication.