Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the α- and β-globin gene loci, the antigen receptor loci, the imprinted H19–Igf2 locus and the Hox gene clusters. Collectively, these studies show that regulatory DNA sequences physically contact genes to control their transcription. Proteins set up the 3D configuration of the genome and we will discuss the roles of the key structural organizers CTCF and cohesin, the nuclear lamina and the transcription machinery. Finally, genes adopt non-random positions in the nuclear interior. We will review studies on gene positioning and propose that cell-specific genome conformations can juxtapose a regulatory sequence on one chromosome to a responsive gene on another chromosome to cause altered gene expression in subpopulations of cells.
Keywords: chromatin domains, gene expression, nuclear organization, genome structure, nuclear periphery
Citation: Holwerda S and de Laat W (2012) Chromatin loops, gene positioning, and gene expression. Front. Gene. 3:217. doi: 10.3389/fgene.2012.00217
Received: 17 July 2012; Paper pending published: 17 August 2012;
Accepted: 01 October 2012; Published online: 17 October 2012.
Edited by:Michèle Amouyal, Centre National de la Recherche Scientifique, France
Reviewed by:Piroska E. Szabo, Beckman Research Institute of City of Hope, USA
Copyright: © 2012 Holwerda and de Laat. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Wouter de Laat, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands. e-mail: email@example.com