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

First Author  Mazzoni EO Year  2013
Journal  Nat Neurosci Volume  16
Issue  9 Pages  1191-1198
PubMed ID  23955559 Mgi Jnum  J:203837
Mgi Id  MGI:5528914 Doi  10.1038/nn.3490
Citation  Mazzoni EO, et al. (2013) Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals. Nat Neurosci 16(9):1191-8
abstractText  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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