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Fig. 7. The Hox-RAR feedback circuit. Cartoon shows the Hox-responsive enhancers
(HOX, green) and RA-responsive enhancers (RARE, blue) from Rarb
(top), Hoxb4 (middle) and Hoxd4 (bottom). Enhancer-promoter
interactions (black arrows), transcription and translation (unfilled arrows),
and transcriptional regulation by Hoxb4 and Hoxd4 proteins (green arrows) and
RARs (blue arrows) are shown. The external RA signal that initiates this
neural genetic circuit (red arrow) is synthesized by Raldh2 in the adjacent
mesoderm. A functional equivalent of the LNE/distal enhancer (HOX element with
broken outline) has, thus far, not been identified for Hoxd4
(Nolte et al., 2003). The
correct positioning of the single or multiple transcription start sites of
each gene has been omitted for clarity. The central importance of the
Hox
RARß interactions described in this study are emphasized with
thick green arrows. This figure also summarizes genetic interactions
identified in several other published studies (see text for details).
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