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Nat Neurosci. 2013 Sep;16(9):1191-1198. doi: 10.1038/nn.3490. Epub 2013 Aug 18.

Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals.

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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.
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.
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Contributed equally


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.

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