Embryonic stem cell-based system for mapping developmental transcriptional programs

Abstract

Presented is a study of gene regulation during development using a combination of chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) and directed differentiation of mouse embryonic stem cells inducibly expressing epitope-tagged transcription factors. The study of developmentally regulated transcription factors by chromatin immunoprecipitation and deep sequencing (ChIP-seq) faces two major obstacles: availability of ChIP-grade antibodies and access to sufficient number of cells. We describe versatile genome-wide analysis of transcription-factor binding sites by combining directed differentiation of embryonic stem cells and inducible expression of tagged proteins. We demonstrate its utility by mapping DNA-binding sites of transcription factors involved in motor neuron specification.