Chromatin folding and gene expression: new tools to reveal the spatial organization of genes.

An important aim in biology is to understand how gene expression is regulated in the context of chromatin. Much progress has been made towards cracking the 'histone code', which describes the composition and organization of chromatin at high resolution. At the lower resolution provided by microscopy, nuclear compartmentalization has been linked to the control of gene expression and silencing. I will review two new techniques able to reveal the three-dimensional organization of individual loci, providing a view of the folding of the chromatin fibre at an intermediate level of resolution. Carter and colleagues and Tolhuis and colleagues have used the new techniques to demonstrate direct physical contact between the locus control region (LCR) and expressed genes in the active murine beta-globin locus. The techniques will allow us to assess the role of locus organization when transcription is directed by distant regulatory elements. The new techniques (and their foreseeable descendants) will permit investigation of many genomic activities involving physical contact between separate regions of any genome. As such, they provide us with a new level of resolution at which to investigate the functional significance of chromatin organization as patterns of gene expression are initiated and modulated during development.