Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation.

ABSTRACT: Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created six-finger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP-seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ∼ 5-fold, with a majority of the new sites locate

SUBMITTER: Grimmer MR 

PROVIDER: S-EPMC4176344 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature