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¹ Medical Research Council Molecular Haematology Unit and ² Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, England, UK
³ Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH9 3JQ, Scotland, UK

Correspondence to Veronica J. Buckle: veronica.buckle{at}imm.ox.ac.uk

Genes on different chromosomes can be spatially associated in the nucleus in several transcriptional and regulatory situations; however, the functional significance of such associations remains unclear. Using human erythropoiesis as a model, we show that five cotranscribed genes, which are found on four different chromosomes, associate with each other at significant but variable frequencies. Those genes most frequently in association lie in decondensed stretches of chromatin. By replacing the mouse -globin gene cluster in situ with its human counterpart, we demonstrate a direct effect of the regional chromatin environment on the frequency of association, whereas nascent transcription from the human -globin gene appears unaffected. We see no evidence that cotranscribed erythroid genes associate at shared transcription foci, but we do see stochastic clustering of active genes around common nuclear SC35-enriched speckles (hence the apparent nonrandom association between genes). Thus, association between active genes may result from their location on decondensed chromatin that enables clustering around common nuclear speckles.

Abbreviations used in this paper: BAC, bacterial artificial chromosome; BrUTP, bromo-UTP; CTD, carboxy-terminal domain; DRB, 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside; ERAF, erythroid-associated factor; M-FISH, multicolor FISH; MIG, mitotic interchromatin granule; RNApolII, RNA polymerase II.

© 2008 Brown et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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