title: NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program.
abstract: Cell fate specification relies on the action of critical transcription factors that become available at distinct stages of embryonic development. One such factor is NeuroD1, which is essential for eliciting the neuronal development program and possesses the ability to reprogram other cell types into neurons. Given this capacity, it is important to understand its targets and the mechanism underlying neuronal specification. Here, we show that NeuroD1 directly binds regulatory elements of neuronal genes that are developmentally silenced by epigenetic mechanisms. This targeting is sufficient to initiate events that confer transcriptional competence, including reprogramming of transcription factor landscape, conversion of heterochromatin to euchromatin, and increased chromatin accessibility, indicating potential pioneer factor ability of NeuroD1. The transcriptional induction of neuronal fate genes is maintained via epigenetic memory despite a transient NeuroD1 induction during neurogenesis. NeuroD1 also induces genes involved in the epithelial-to-mesenchymal transition, thereby promoting neuronal migration. Our study not only reveals the NeuroD1-dependent gene regulatory program driving neurogenesis but also increases our understanding of how cell fate specification during development involves a concerted action of transcription factors and epigenetic mechanisms.
authors.affiliation: Institute of Molecular Biology (IMB), Mainz, Germany.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Pataskar
authors.affiliation: Institute of Molecular Biology (IMB), Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Jung
authors.affiliation: Adolf Butenandt Institute and Center for Integrated Protein Science, Ludwig Maximilian University, Munich, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Smialowski
authors.affiliation: DFG-Research Center for Regenerative Therapies, Cluster of Excellence, TU-Dresden, Dresden, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Noack
authors.affiliation: DFG-Research Center for Regenerative Therapies, Cluster of Excellence, TU-Dresden, Dresden, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Calegari
authors.affiliation: Adolf Butenandt Institute and Center for Integrated Protein Science, Ludwig Maximilian University, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Straub
authors.affiliation: Institute of Molecular Biology (IMB), Mainz, Germany v.tiwari@imb-mainz.de.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D051379:Mice; D009474:Neurons / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D014157:Transcription Factors; C501008:Neurod1 protein, mouse
keywords: NeuroD1; epigenetics; gene regulation; neurogenesis; pioneer transcription factor