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Publication : Bimodal control of Hoxd gene transcription in the spinal cord defines two regulatory subclusters.

First Author  Tschopp P Year  2012
Journal  Development Volume  139
Issue  5 Pages  929-39
PubMed ID  22278926 Mgi Jnum  J:182758
Mgi Id  MGI:5316548 Doi  10.1242/dev.076794
Citation  Tschopp P, et al. (2012) Bimodal control of Hoxd gene transcription in the spinal cord defines two regulatory subclusters. Development 139(5):929-39
abstractText  The importance of Hox genes in the specification of neuronal fates in the spinal cord has long been recognized. However, the transcriptional controls underlying their collinear expression domains remain largely unknown. Here we show in mice that the correspondence between the physical order of Hoxd genes and their rostral expression boundaries, although respecting spatial collinearity, does not display a fully progressive distribution. Instead, two major anteroposterior boundaries are detected, coinciding with the functional subdivision of the spinal cord. Tiling array analyses reveal two distinct blocks of transcription, regulated independently from one another, that define the observed expression boundaries. Targeted deletions in vivo that remove the genomic fragments separating the two blocks induce ectopic expression of posterior genes. We further evaluate the independent regulatory potential and transcription profile of each gene locus by a tiling array approach using a contiguous series of transgenes combined with locus-specific deletions. Our work uncovers a bimodal type of HoxD spatial collinearity in the developing spinal cord that relies on two separate 'enhancer mini-hubs' to ensure correct Hoxd gene expression levels while maintaining their appropriate anteroposterior boundaries.
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