title: Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1.
abstract: Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined. Here, we identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. We determined how Geminin deficiency affected histone acetylation at gene promoters during this process. We integrated these data to demonstrate that Geminin associates with and promotes histone acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system-enriched expression and encode other regulators of neural development. Both Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs, while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co-regulatory potential. Accordingly, we found that Geminin and Zic1 could cooperatively activate the expression of several shared targets encoding transcription factors that control neurogenesis, neural plate patterning, and neuronal differentiation. We used these data to construct gene regulatory networks underlying neural fate acquisition. Establishment of this molecular program in nascent neuroectoderm directly links early neural cell fate acquisition with regulatory control of later neurodevelopment.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Sankar
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Yellajoshyula
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Teets
authors.affiliation: Department of Genetics, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rockweiler
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Kroll
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004622:Embryo, Mammalian; D064248:Geminin / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D016678:Genome; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058977:Molecular Sequence Annotation; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D054258:Neural Plate / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D064248:Geminin; C577997:Gmnn protein, mouse; D006657:Histones; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse; D014157:Transcription Factors; C492122:Zic1 protein, mouse