Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions

Abstract

The regulation of gene expression is mediated by interactions between chromatin and protein complexes. The importance of where and when these interactions take place in the nucleus is currently a subject of intense investigation. Increasing evidence indicates that gene activation or silencing is often associated with repositioning of the locus relative to nuclear compartments and other genomic loci. At the same time, however, structural constraints impose limits on chromatin mobility. Understanding how the dynamic nature of the positioning of genetic material in the nuclear space and the higher-order architecture of the nucleus are integrated is therefore essential to our overall understanding of gene regulation.

Parental genomes mix in mule and human cell nuclei

“…The spatial organization of the genome in the nucleus has come into focus as an important level of epigenetic regulation (for reviews, see Kosak and Groudine 2004;Lanctôt et al 2007;Misteli 2007). However, basic essential questions are still unanswered, such as whether chromosomes inherited from mother and father are separated in the nucleus.…”

Repeated elements coordinate the spatial organization of the yeast genome

“…Genome architecture is dynamic (Lanctot et al, 2007, and references therein) and nucleolar structure is dependent upon transcription (Haaf and Ward, 1996). Therefore, we reasoned that the distribution of the ETS2 domain-genome interaction zones would be affected by the absence of transcription.…”

“…It is clear that the spatial arrangement of the genome into subcompartments is important for the regulation of developmental and cellular processes (Chakalova et al, 2005;Dostie et al, 2006;Foster and Bridger, 2005;Lanctot et al, 2007;Ling et al, 2006;Spilianakis et al, 2005;Zhao et al, 2006). However, we currently do not know how nuclear subcompartments are formed.…”

“…Intra-and interchromosomal interactions (Gerasimova et al, 2000;Lanctot et al, 2007;Simonis et al, 2006;Xu et al, 2004), mediated by macromolecular complexes comprising proteins and nucleic acids, provide one mechanism by which the genome could be spatially arranged into functional subcompartments. This potential is exemplified by the fact that the interacting DNA sequences are often not linearly arranged or even on the same chromosome (Dostie et al, 2006;Ling et al, 2006;O'Sullivan et al, 2004;Simonis et al, 2006;Spilianakis et al, 2005;Zhao et al, 2006).…”

L’hétérochromatine constitutive dans tous ses états

“…Plusieurs études ont ainsi montré le repositionnement nucléaire de locus dans des processus de différenciation associés à des changements d'expression des gènes. L'hétérochromatine péricentrique, en particulier, joue un rôle important pour l'inactivation du locus brown dans les embryons de drosophile [26] et pourrait être nécessaire au maintien de l'état transcriptionnellement inactif de certains gènes au cours de la différenciation lymphocytaire chez la souris (pour revues [27,40]. Au-delà de son rôle dans la régulation stable et transmissible à la descendance des patrons d'expression de certains gènes, plusieurs études ont par ailleurs récemment démontré que l'hétérochromatine péri-centromérique pourrait être impliquée dans le phénomène d'exclusion allélique, responsable de l'expression mono-allélique des gènes d'immunoglobuline et par conséquent de la spécificité immunologique des lymphocytes B [28].…”