Nuclear re-organisation of theHoxbcomplex during mouse embryonic development

Abstract

The spatial and temporal co-linear expression of Hox genes during development is an exquisite example of programmed gene expression. The precise mechanisms underpinning this are not known. Analysis of Hoxbchromatin structure and nuclear organisation, during the differentiation of murine ES cells, has lent support to the idea that there is a progressive`opening' of chromatin structure propagated through Hox clusters from 3′to 5′, which contributes to the sequential activation of gene expression. Here, we show that similar events occur in vivo in at least two stages of development. The first changes in chromatin structure and nuclear organisation were detected during gastrulation in the Hoxb1-expressing posterior primitive streak region: Hoxbchromatin was decondensed and the Hoxb1 locus looped out from its chromosome territory, in contrast to non-expressing Hoxb9, which remained within the chromosome territory. At E9.5, when differential Hox expression along the anteroposterior axis is being established, we found concomitant changes in the organisation of Hoxb. Hoxb organisation differed between regions of the neural tube that had never expressed Hoxb [rhombomeres (r) 1 and 2], strongly expressed Hoxb1 but not b9 (r4), had downregulated Hoxb1 (r5), expressed Hoxb9 but not Hoxb1 (spinal cord), and expressed both genes(tail bud). We conclude that Hoxb chromatin decondensation and nuclear re-organisation is regulated in different parts of the developing embryo, and at different developmental stages. The differential nuclear organisation of Hoxb along the anteroposterior axis of the developing neural tube is coherent with co-linear Hox gene expression. In early development nuclear re-organisation is coupled to Hoxb expression,but does not anticipate it.

Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation

“…The role of chromatin in regulating Hox gene transcriptional initiation has recently come under the spotlight through studies showing sequential 3Ј to 5Ј chromatin decondensation of the HoxB cluster during mouse embryonic development (5,50) and regulation of HoxD gene expression through chromatin remodeling during limb development (51) and neural differentiation (33). In this study, we showed that nucleosomes are positioned at the Hoxd4 P1 promoter and are remodeled following RA treatment of P19 cells.…”

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

“…What determines which RAresponsive genes are available to be expressed at a given time is the subject of ongoing studies. Recent work has shown that, within a Hox cluster, the timing of hindbrain expression may be regulated by the progressive opening of chromatin rather than the local accumulation of active transacting factors (Chambeyron et al, 2005).…”

Cell Type–Specific Chromatin Decondensation of a Metabolic Gene Cluster in Oats

“…In mammalian systems, transcription-related chromatin decondensation has been observed in a number of artificial gene clusters, in highly transcribed chromosomal regions and for clusters of functionally related genes that are coordinately regulated during development or between different cells types, such as the Hoxb locus (Tumbar et al, 1999;Tsukamoto et al, 2000;Volpi et al, 2000;Williams et al, 2002;Chambeyron and Bickmore, 2004;Janicki et al, 2004;Chambeyron et al, 2005;Sproul et al, 2005;Morey et al, 2007). In plants, genes are normally considered to be randomly distributed throughout the genome, with the obvious exception of groups of physically linked genes that share sequence homology and that have arisen through tandem gene duplication (e.g., gene-for-gene type disease resistance genes) (Friedman and Baker, 2007).…”