title: Ectopic nuclear reorganisation driven by a Hoxb1 transgene transposed into Hoxd.
abstract: The extent to which the nuclear organisation of a gene impacts on its ability to be expressed, or whether nuclear organisation merely reflects gene expression states, remains an important but unresolved issue. A model system that has been instrumental in investigating this question utilises the murine Hox gene clusters encoding homeobox-containing proteins. Nuclear reorganisation and chromatin decondensation, initiated towards the 3' end of the clusters, accompanies activation of Hox genes in both differentiation and development, and might be linked to mechanisms underlying colinearity. To investigate this, and to delineate the cis-acting elements involved, here we analyse the nuclear behaviour of a 3' Hoxb1 transgene transposed to the 5' end of the Hoxd cluster. We show that this transgene contains the cis-acting elements sufficient to initiate ectopic local nuclear reorganisation and chromatin decondensation and to break Hoxd colinearity in the primitive streak region of the early embryo. Significantly, in rhombomere 4, the transgene is able to induce attenuated nuclear reorganisation and decondensation of Hoxd even though there is no detectable expression of the transgene at this site. This shows that reorganisation of chromosome territories and chromatin decondensation can be uncoupled from transcription itself and suggests that they can therefore operate upstream of gene expression.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh University, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Céline
authors.initials: C
authors.lastname: Morey
authors.forename: Nelly R
authors.initials: NR
authors.lastname: Da Silva
authors.forename: Marie
authors.initials: M
authors.lastname: Kmita
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics* / Q000648:ultrastructure; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D018878:Limb Buds / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D054240:Primitive Streak / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D019076:Transgenes / Q000235:genetics*
chemical_list: D002843:Chromatin; D004251:DNA Transposable Elements; C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; C486697:Hoxd1 protein, mouse