Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci

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Science  21 Nov 2014:
Vol. 346, Issue 6212, pp. 1004-1006
DOI: 10.1126/science.1257493

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Hox genes are required during the morphogenesis of both vertebrate digits and external genitals. We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal. We propose that this convergent regulatory evolution was triggered by the preexistence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates.

Similar regulation of digit and genital development

Hox proteins help set up the vertebrate and invertebrate body plan and also specify segment identity, such as leg versus antennae. Lonfat et al. examined Hox gene regulation in mouse limb and genitals. Although the limb and genitals have widely differing structure and function, they display common features for Hox regulation during development. Transcription at these anatomical sites depends upon gene enhancers within a shared chromatin topological domain. It is likely that this regulatory landscape provided genomic niches for enhancer evolution.

Science, this issue p. 1004

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