title: Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals.
abstract: Hox genes controlling motor neuron subtype identity are expressed in rostrocaudal patterns that are spatially and temporally collinear with their chromosomal organization. Here we demonstrate that Hox chromatin is subdivided into discrete domains that are controlled by rostrocaudal patterning signals that trigger rapid, domain-wide clearance of repressive histone H3 Lys27 trimethylation (H3K27me3) polycomb modifications. Treatment of differentiating mouse neural progenitors with retinoic acid leads to activation and binding of retinoic acid receptors (RARs) to the Hox1-Hox5 chromatin domains, which is followed by a rapid domain-wide removal of H3K27me3 and acquisition of cervical spinal identity. Wnt and fibroblast growth factor (FGF) signals induce expression of the Cdx2 transcription factor that binds and clears H3K27me3 from the Hox1-Hox9 chromatin domains, leading to specification of brachial or thoracic spinal identity. We propose that rapid clearance of repressive modifications in response to transient patterning signals encodes global rostrocaudal neural identity and that maintenance of these chromatin domains ensures the transmission of positional identity to postmitotic motor neurons later in development.
authors: Departments of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University Medical Center, 630 W 168 Street, New York, NY 10032, USA.|Department of Biology, New York University. 100 Washington Square East, New York, NY 10003, USA.
authors: Esteban O
authors: EO
authors: Mazzoni
authors: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA.|Department of Biochemistry & Molecular Biology, Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802.
authors: Shaun
authors: S
authors: Mahony
authors: Departments of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University Medical Center, 630 W 168 Street, New York, NY 10032, USA.
authors: Mirza
authors: M
authors: Peljto
authors: Departments of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University Medical Center, 630 W 168 Street, New York, NY 10032, USA.
authors: Tulsi
authors: T
authors: Patel
authors: Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors: Seraphim R
authors: SR
authors: Thornton
authors: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors: Scott
authors: S
authors: McCuine
authors: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA.
authors: Christopher
authors: C
authors: Reeder
authors: Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors: Laurie A
authors: LA
authors: Boyer
authors: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors: Richard A
authors: RA
authors: Young
authors: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA.
authors: David K
authors: DK
authors: Gifford
authors: Departments of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University Medical Center, 630 W 168 Street, New York, NY 10032, USA.
authors: Hynek
authors: H
authors: Wichterle
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D001921:Brain / Q000166:cytology; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009088:Mucoproteins / Q000235:genetics; D058953:Neural Stem Cells / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D002843:Chromatin; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D009088:Mucoproteins; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; C010393:lysin, gastropoda; D014212:Tretinoin; D005346:Fibroblast Growth Factors
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