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Title

Mechanisms of "Hoxd" genes collinearity in developing digits and external genitalia

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Defense Thèse de doctorat : Univ. Genève, 2007 - Sc. 3944 - 2007/09/26
Abstract During the development of mammalian digits, clustered "Hoxd" genes are expressed following a collinear strategy, such that their expression levels correlate with gene order in the complex. By analyzing the distribution of transcript levels and the spatial organization of the "HoxD" locus in a variety of genetic configurations, we found that the locus adopts an active conformation in digits, bringing two distant enhancers in physical proximity with the 5' extremity of the complex. These interactions result in the polar activation of the locus, gene rank relative to the 5' extremity of the cluster controlling the respective expression levels. This remote regulation is accompanied by a widespread intergenic transcription in the posterior "HoxD" complex, leading to the synthesis of various non-coding RNAs of unknown function. Furthermore, as similar analysis of transcript levels distribution in the genital bud suggests a common regulatory mechanism for "HoxD" genes in digits and external genitalia.
Keywords LimbsGenitalsRegulatory landscapesLooping
Stable URL https://archive-ouverte.unige.ch/unige:1475
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URN: urn:nbn:ch:unige-14754
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Deposited on : 2009-05-05

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