A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

ABSTRACT: Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron

SUBMITTER: Velasco S 

PROVIDER: S-EPMC5291817 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature