Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription.
The colinearity of genes in Hox clusters suggests a role for chromosome structure in gene regulation. We reveal programmed changes in chromatin structure and nuclear organization upon induction of Hoxb expression by retinoic acid. There is an early increase in the histone modifications that are marks of active chromatin at both the early expressed gene Hoxb1, and also at Hoxb9 that is not expressed until much later. There is also a visible decondensation of the chromatin between Hoxb1 and Hoxb9 at this early stage. However, a further change in higher-order chromatin structure, looping out of genes from the chromosome territory, occurs in synchrony with the execution of the gene expression program. We suggest that higher-order chromatin structure regulates the expression of the HoxB cluster at several levels. Locus-wide changes in chromatin structure (histone modification and chromatin decondensation) may establish a transcriptionally poised state but are not sufficient for the temporal program of gene expression. The choreographed looping out of decondensed chromatin from chromosome territories may then allow for activation of high levels of transcription from the sequence of genes along the cluster.
Chambeyron
Séverine
S
MRC Human Genetics Unit, Edinburgh EH4 2XU, United Kingdom.
Bickmore
Wendy A
WA
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D020223:Chromosome Painting; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005801:Genes, Homeobox; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D005810:Multigene Family; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D002843:Chromatin; C101121:HOXB1 homeodomain protein; D006657:Histones; D018398:Homeodomain Proteins; C104161:Hoxb9 protein, mouse; D014212:Tretinoin; D004247:DNA