Genetic analysis of a conserved sequence in theHoxD complex: Regulatory redundancy or limitations of the transgenic approach?

Beckers, Johannes; Duboule, Denis

doi:10.1002/(sici)1097-0177(199809)213:1<1::aid-aja1>3.0.co;2-l

Cited by 29 publications

(2 citation statements)

References 57 publications

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“…What tracker considers to be multiple footprints may correspond to a single potential ncRNA gene, as indicated by alignment of the region between Hoxd-11 and Hoxd-10 with the corresponding ESTs (not shown). Two of the expressed footprints were previously identified as regulatory regions RVIII/RIX (fp26) and RX (fp20) ([52-55]. The fact that these two regulatory regions appear to be transcribed may shed new light on how they function.…”

Section: Resultsmentioning

confidence: 99%

Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

2010

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BackgroundThe posterior genes of the HoxD cluster play a crucial role in the patterning of the tetrapod limb. This region is under the control of a global, long-range enhancer that is present in all vertebrates. Variation in limb types, as is the case in amphibians, can probably not only be attributed to variation in Hox genes, but is likely to be the product of differences in gene regulation. With a collection of vertebrate genome sequences available today, we used a comparative genomics approach to study the posterior HoxD cluster of amphibians. A frog and a caecilian were included in the study to compare coding sequences as well as to determine the gain and loss of putative regulatory sequences.ResultsWe sequenced the posterior end of the HoxD cluster of a caecilian and performed comparative analyses of this region using HoxD clusters of other vertebrates. We determined the presence of conserved non-coding sequences and traced gains and losses of these footprints during vertebrate evolution, with particular focus on amphibians. We found that the caecilian HoxD cluster is almost three times larger than its mammalian counterpart. This enlargement is accompanied with the loss of one gene and the accumulation of repeats in that area. A similar phenomenon was observed in the coelacanth, where a different gene was lost and expansion of the area where the gene was lost has occurred. At least one phylogenetic footprint present in all vertebrates was lost in amphibians. This conserved region is a known regulatory element and functions as a boundary element in neural tissue to prevent expression of Hoxd genes.ConclusionThe posterior part of the HoxD cluster of Typhlonectes natans is among the largest known today. The loss of Hoxd-12 and the expansion of the intergenic region may exert an influence on the limb enhancer, by having to bypass a distance seven times that of regular HoxD clusters. Whether or not there is a correlation with the loss of limbs remains to be investigated. These results, together with data on other vertebrates show that the tetrapod Hox clusters are more variable than previously thought.

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Section: Resultsmentioning

confidence: 99%

Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

2010

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“…For instance, an element from the human HOXD cluster was recently reported to bind PcG proteins and to induce repression of a reporter gene [49]. However, the deletion of the murine orthologous sequence did not cause any dramatic change in Hoxd gene regulation [50], suggesting that it is not critical for PcG recruitment or, alternatively, that it is part of a robust mechanism with high compensatory capacities. Interestingly, CG-rich sequences, which are particularly abundant within Hox clusters, were proposed as a hallmark of PcG target promoters, at least in ES cells [51,52].…”

Section: Epigenetic Control By Polycomb and Trithorax Complexesmentioning

confidence: 99%

Chromatin organization and global regulation ofHoxgene clusters

Montavon

Duboule

2013

Phil. Trans. R. Soc. B

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During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological organization of Hox clusters and their transcriptional activation in space and time has served as a paradigm for understanding the relationships between genome structure and function. Here, we review some recent observations, which revealed highly dynamic changes in the structure of chromatin at Hox clusters, in parallel with their activation during embryonic development. We discuss the relevance of these findings for our understanding of large-scale gene regulation.

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Dynamics of Polycomb and Trithorax activities during development

Soshnikova

2011

Birth Defects Research

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Dynamic changes in gene expression are tightly controlled during development, as a single totipotent zygote gives rise to distinct cell lineages. The establishment and maintenance of these diverse transcriptional programs rely on changes of chromatin state, mainly through histone modifications. Polycomb and Trithorax complexes participate in setting apart active and inactive genes by respectively repressing and activating key developmental regulators in different cell types. Over the last decade, our understanding of the biochemical mechanisms underlying their activities has greatly improved, but the signals targeting these proteins to specific regions of the genome are still poorly understood, particularly in vertebrates. Recent findings highlight the highly dynamic activities of Polycomb and Trithorax complexes in vivo. Surprisingly, although their role in transcriptional regulation is deeply conserved during evolution, the time sequence in which they act seems to vary across species.

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Genetic analysis of a conserved sequence in theHoxD complex: Regulatory redundancy or limitations of the transgenic approach?

Cited by 29 publications

References 57 publications

Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

Chromatin organization and global regulation ofHoxgene clusters

Dynamics of Polycomb and Trithorax activities during development

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