Aug 9, 2012

Anterior-posterior differences in HoxD chromatin topology in limb development

Development
Iain WilliamsonWendy A Bickmore

Abstract

A late phase of HoxD activation is crucial for the patterning and growth of distal structures across the anterior-posterior (A-P) limb axis of mammals. Polycomb complexes and chromatin compaction have been shown to regulate Hox loci along the main body axis in embryonic development, but the extent to which they have a role in limb-specific HoxD expression, an evolutionary adaptation defined by the activity of distal enhancer elements that drive expression of 5' Hoxd genes, has yet to be fully elucidated. We reveal two levels of chromatin topology that differentiate distal limb A-P HoxD activity. Using both immortalised cell lines derived from posterior and anterior regions of distal E10.5 mouse limb buds, and analysis in E10.5 dissected limb buds themselves, we show that there is a loss of polycomb-catalysed H3K27me3 histone modification and a chromatin decompaction over HoxD in the distal posterior limb compared with anterior. Moreover, we show that the global control region (GCR) long-range enhancer spatially colocalises with the 5' HoxD genomic region specifically in the distal posterior limb. This is consistent with the formation of a chromatin loop between 5' HoxD and the GCR regulatory module at the time and place of dist...Continue Reading

  • References38
  • Citations24

References

  • References38
  • Citations24

Citations

Mentioned in this Paper

Fluorescent in Situ Hybridization
Chromatin Loop
Genome
Complex (molecular entity)
Coinfection
Kinetic Polymerase Chain Reaction
Immunofluorescence Microscopy
Embryonic Development
Chromatin Immunoprecipitation
Limb Structure

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