Sequentially acting Sox transcription factors in neural lineage development
- Maria Bergsland1,
- Daniel Ramsköld1,
- Cécile Zaouter,
- Susanne Klum,
- Rickard Sandberg2 and
- Jonas Muhr2,3
- Ludwig Institute for Cancer Research, Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
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.
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Footnotes
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↵3 Corresponding author.
E-mail jonas.muhr{at}licr.ki.se.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.176008.111.
- Received August 2, 2011.
- Accepted October 13, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press