Major: Molecular Biology
Research Department: Microbiology/ Gene Regulation Graduation Date: May 2018 Abstract: Transcription is a highly regulated process that consists of initiation, elongation, and termination.1 Many proteins play an important role in the regulation of elongation, thereby regulating gene expression. RNA Polymerase ll (pol ll) pauses after transcribing about 20-60 base pairs of RNA by the effect of negative elongation factors (such as NELF and DSIF) and nucleosome barriers. Using its kinase activity, the P-TEFb kinase is involved in releasing this pause step by phosphorylating the carboxy-terminal domain (CTD) of pol ll as well as the negative elongation factors previously mentioned. P-TEFb is found catalytically inactive when bound to the 7SK complex, but found active when released from this complex. While it is still unclear how P-TEFb is dislodged from the 7SK complex, the D’Orso lab has found that KAP1, a transcriptional regulator, recruits the 7SK complex along with inactive P-TEFb to paused pol ll.3 ChIp-Seq data also shows that KAP1 and the 7SK complex co-occupy most genes containing paused pol ll, suggesting genome-wide binding.1 Prior to this knowledge, KAP1 was primarily identified to play a repressive role in gene expression, but this suggests an interesting activating role for the protein. Yet, It is still unclear how KAP1 itself is recruited to chromatin. Here we report that KAP1 may bind to a novel H4 histone mark, H4R3me1 +Kac, suggesting that this mark plays a role in activation and is one of the mechanisms by which KAP1 is recruited to chromatin to activate transcription. |
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