IDENTIFICATION OF ESSENTIAL CIS-REGULATROY ELEMENTS FOR PLURIPOTENCY BY CRISPR SCREEN

Abstract

The Cis-regulatory elements were found to play an important role in governing the cell identity by regulating distinct transcription profile in different cell types. A hallmark of the cis-regulatory elements is that they can regulate their target genes expression independent of its orientation and distance to their target genes. Here, we describe a systematic CRISPR/Cas9 screen for functional OCT4 bound cis regulatory elements in mouse ES cells. Through the screen, we are able to identify several cis regulatory elements that are important for the maintenance of pluripotency and self-renew in ES cells. Chromatin capture assay on the candidate cis-regulatory elements identified their target genes and uncovers a complex network connecting master transcription factor, Oct4, and cis-regulatory elements in maintaining of ES cell pluripotency.