The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis
Autor: | Johannes M. Thalhammer, Simone Reiprich, Anne Jacob, Michael Wegner, Elisabeth Sock, Elli-Anna Balta, D. Chichung Lie, Melanie Küspert, Franziska Fröb, Hannah M Wüst |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Chromatin Immunoprecipitation Neural Tube Neurogenesis Green Fluorescent Proteins Electrophoretic Mobility Shift Assay Mice Transgenic Nerve Tissue Proteins Chick Embryo Biology Biochemistry SOXC Transcription Factors Mice 03 medical and health sciences Cellular and Molecular Neuroscience PROX1 Gene Prosencephalon Neural Stem Cells Tubulin medicine Transcriptional regulation Animals Enhancer Transcription factor Homeodomain Proteins Tumor Suppressor Proteins Neural tube Computational Biology Gene Expression Regulation Developmental Embryo Mammalian Cell biology Mice Inbred C57BL Electroporation Gene Ontology 030104 developmental biology medicine.anatomical_structure POU Domain Factors Homeobox |
Zdroj: | Journal of Neurochemistry. 146:251-268 |
ISSN: | 0022-3042 |
DOI: | 10.1111/jnc.14456 |
Popis: | The high-mobility-group domain containing SoxC transcription factors Sox4 and Sox11 are expressed and required in the vertebrate central nervous system in neuronal precursors and neuroblasts. To identify genes that are widely regulated by SoxC proteins during vertebrate neurogenesis we generated expression profiles from developing mouse brain and chicken neural tube with reduced SoxC expression and found the transcription factor prospero homeobox protein 1 (Prox1) strongly down-regulated under both conditions. This led us to hypothesize that Prox1 expression depends on SoxC proteins in the developing central nervous system of mouse and chicken. By combining luciferase reporter assays and over-expression in the chicken neural tube with in vivo and in vitro binding studies, we identify the Prox1 gene promoter and two upstream enhancers at -44 kb and -40 kb relative to the transcription start as regulatory regions that are bound and activated by SoxC proteins. This argues that Prox1 is a direct target gene of SoxC proteins during neurogenesis. Electroporations in the chicken neural tube furthermore show that Prox1 activates a subset of SoxC target genes, whereas it has no effects on others. We propose that the transcriptional control of Prox1 by SoxC proteins may ensure coupling of two types of transcription factors that are both required during early neurogenesis, but have at least in part distinct functions. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/. |
Databáze: | OpenAIRE |
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