@article{4553022e38ad4b26ad6c279456939cca,
title = "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 enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic.",
author = "Silvia Velasco and Ibrahim, {Mahmoud M.} and Akshay Kakumanu and G{\"o}rkem Garipler and Beg{\"u}m Aydin and Al-Sayegh, {Mohamed Ahmed} and Antje Hirsekorn and Farah Abdul-Rahman and Rahul Satija and Uwe Ohler and Shaun Mahony and Mazzoni, {Esteban O.}",
note = "Funding Information: This work was supported by R01HD079682 NICHD, 5-FY14-99 March of Dimes, Project ALS (A13-0416) to E.O.M., and DP2-HG-009623 to R.S. M.M.I. is supported by the MDC-NYU exchange program. M.M.I. and U.O. were in part supported by the Simons Foundation, through participation in the Spring 2016 Program on Algorithmic Challenges in Genomics at the Simons Institute for Theoretical Computing, UC Berkeley. S.M. is supported by the Center for Eukaryotic Gene Regulation at Pennsylvania State University. The authors would like to thank Hyoju Ban and Ashley Nicole Powers for their help with single cell RNA-seq experiments; Wanjing Huo for help in molecular biology; and the NYU Gencore and FACS-sorting Facilities. Also, we would like to thank Lionel Christiaen, Kenneth Birnbaum, and Eftychia Apostolou for suggestions and Scott Lacadie for the template of the nucleosome-DNA cartoons. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = feb,
day = "2",
doi = "10.1016/j.stem.2016.11.006",
language = "English (US)",
volume = "20",
pages = "205--217.e8",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}