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Fig. 8. Global regulation of Hoxd gene cluster. (Left) The sequential activation of 3' to 5' Hoxd genes is shown from the hypothesised global early enhancer (EE) that mediates the temporally co-linear activation of the Hoxd genes along the main axis. The EE in the scheme corresponds to the ELCR (early limb control region) postulated by Zákány and colleagues (Zákány et al., 2004). (Right) The regulatory influence of the 5' global control region (GCR) on the Hoxd cluster and neighbouring genes in the digits (green) and neural tube (grey). A timescale is depicted below. The activation times of the Hoxd genes is shown for only three genes: Hoxd1 (yellow), Hoxd8 (orange) and Hoxd13 (brown). The action of the GCR is stronger on the most 5' gene Hoxd13 (thicker green arrow) than on Hoxd12 to Hoxd10. ins, insulator in neural tissues. Lnp, lunapark; Evx2, mouse even-skipped homolog 2.





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