Research Theme:

Understanding the regulation of chromatin accessibility by KRAB-ZFPs through high-resolution profiling and rapid depletion of their co-factor KAP1

Research Summary:

Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs) are a large family of transcription factors found in higher vertebrates. The most-well described function of KRAB-ZFPs is epigenetic silencing of transposable elements (TEs). The KRAB domain they contain interacts with KAP1, which subsequently recruits effector proteins such as SETDB1 which adds a tri-methylation chromatin mark to lysine 9 of histone 3 (H3K9me3) and the NuRD complex (nucleosome remodelling deacetylase) involved in removing activating chromatin marks. 

This project aims to understand the how the differential expression and binding profiles of KRAB-ZFPs contributes to cell-type specific functions. We will do this through directly studying KAP1. We will perform chromatin immunoprecipitation (ChIP) followed by deep sequencing to map all of the actively repressed binding sites of KRAB-ZFPs and make comparisons between cell types. Secondly, we will knockdown KAP1 using an inducible degron system and follow the timeline of events following this by transcriptomic profiling. Together, we will use this information to better understand the repression dynamics by KAP1 and make connections between KRAB-ZFPs and specific cellular processes