title: Sequentially acting Sox transcription factors in neural lineage development.
abstract: Pluripotent embryonic stem (ES) cells can generate all cell types, but how cell lineages are initially specified and maintained during development remains largely unknown. Different classes of Sox transcription factors are expressed during neurogenesis and have been assigned important roles from early lineage specification to neuronal differentiation. Here we characterize the genome-wide binding for Sox2, Sox3, and Sox11, which have vital functions in ES cells, neural precursor cells (NPCs), and maturing neurons, respectively. The data demonstrate that Sox factor binding depends on developmental stage-specific constraints and reveal a remarkable sequential binding of Sox proteins to a common set of neural genes. Interestingly, in ES cells, Sox2 preselects for neural lineage-specific genes destined to be bound and activated by Sox3 in NPCs. In NPCs, Sox3 binds genes that are later bound and activated by Sox11 in differentiating neurons. Genes prebound by Sox proteins are associated with a bivalent chromatin signature, which is resolved into a permissive monovalent state upon binding of activating Sox factors. These data indicate that a single key transcription factor family acts sequentially to coordinate neural gene expression from the early lineage specification in pluripotent cells to later stages of neuronal development.
authors.affiliation: Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bergsland
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramsköld
authors.forename: Cécile
authors.initials: C
authors.lastname: Zaouter
authors.forename: Susanne
authors.initials: S
authors.lastname: Klum
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Muhr
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism; D055747:SOX Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics; D015854:Up-Regulation
chemical_list: D055747:SOX Transcription Factors; D055748:SOXB1 Transcription Factors; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C527783:Sox2 protein, mouse; C527786:Sox3 protein, mouse
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