The constrained architecture of mammalian Hox gene clusters

Darbellay, Fabrice and Bochaton, Célia and Lopez-Delisle, Lucille and Mascrez, Bénédicte and Tschopp, Patrick and Delpretti, Saskia and Zakany, Jozsef and Duboule, Denis. (2019) The constrained architecture of mammalian Hox gene clusters. Proceedings of the National Academy of Sciences, 116 (27). pp. 13424-13433.

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Official URL: https://edoc.unibas.ch/73526/

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In many animal species with a bilateral symmetry,; Hox; genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate; Hox; clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the; HoxD; cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian; Hox; clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of; Hox; clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in; cis; .
Faculties and Departments:05 Faculty of Science > Departement Umweltwissenschaften > Integrative Biologie > Regulatory Evolution (Tschopp)
UniBasel Contributors:Tschopp, Patrick
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Nov 2020 14:15
Deposited On:06 Nov 2020 14:15

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