Project Title:

Assessing the underlying regulatory potential of KRAB-ZFP targets through a large scale analysis of ATAC-seq datasets.

Project Summary:

KRAB zinc finger proteins (KRAB-ZFPs) are the largest group of mammalian transcription factors. They appeared in the common ancestor of coelacanths and tetrapods and have since evolved very rapidly, with new members identified at each evolutionary branch. Their functional activity has been connected with the silencing of transposable elements through formation of heterochromatin. This behaviour was initially thought to have developed to silence these mobile elements and reduce the genomic instability associated with their potential re-insertion. However, many KRAB-ZFPs are conserved and are still binding old transposable elements which have long lost their ability to transpose, due to the accumulation of mutations. This suggests the maintenance of KRAB-ZFPs in the human genome is associated with other functions. This project investigates an alternative hypothesis for the role of KRAB-ZFPs in the human genome, which suggests they are involved in building gene regulatory networks with transposable elements. KRAB-ZFPs are required to silence remnants of transposable elements with promoter- or enhancer-like functions in particular cellular contexts, whereas in others, they are left accessible and participate in gene regulation. To understand this large-scale activity of KRAB-ZFPs and their relationship with their targets, we use human ATAC-seq datasets and find clear differences in chromatin accessibility, as well as different patterns of transposable element and KRAB-ZFP binding sites enrichment.