The nucleus is an ordered three-dimensional entity, and organization of the genome within the nuclear space might have implications for orchestrating gene expression. Recent technological developments have revealed that chromatin is folded into loops bringing distal regulatory elements into intimate contact with the genes that they regulate. Such intrachromosomal contacts appear to be a general mechanism of enhancer-promoter communication in cis. Tantalizing evidence is emerging that regulatory elements might have the capacity to act in trans to regulate genes on other chromosomes. However, unequivocal data required to prove that interchromosomal gene regulation truly represents another level of control within the nucleus is lacking, and this concept remains highly contentious. Such controversy emphasizes that our current understanding of the mechanisms that govern gene expression are far from complete.
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