The β-globin nuclear compartment in development and erythroid differentiation (original) (raw)
- Letter
- Published: 21 September 2003
- Bas Tolhuis1 na1,
- Erik Splinter1,
- Rian Nijmeijer1,
- Frank Grosveld1 &
- …
- Wouter de Laat1
Nature Genetics volume 35, pages 190–194 (2003)Cite this article
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Abstract
Efficient transcription of genes requires a high local concentration of the relevant _trans_-acting factors. Nuclear compartmentalization can provide an effective means to locally increase the concentration of rapidly moving _trans_-acting factors; this may be achieved by spatial clustering of chromatin-associated binding sites for such factors1,2,3,4,5. Here we analyze the structure of an erythroid-specific spatial cluster of _cis_-regulatory elements and active β-globin genes, the active chromatin hub (ACH; ref. 6), at different stages of development and in erythroid progenitors. We show, in mice and humans, that a core ACH is developmentally conserved and consists of the hypersensitive sites (HS1–HS6) of the locus control region (LCR), the upstream 5′ HS–60/–62 and downstream 3′ HS1. Globin genes switch their interaction with this cluster during development, correlating with the switch in their transcriptional activity7. In mouse erythroid progenitors that are committed to but do not yet express β-globin, only the interactions between 5′ HS–60/–62, 3′ HS1 and hypersensitive sites at the 5′ side of the LCR are stably present. After induction of differentiation, these sites cluster with the rest of the LCR and the gene that is activated. We conclude that during erythroid differentiation, _cis_-regulatory DNA elements create a developmentally conserved nuclear compartment dedicated to RNA polymerase II transcription of β-globin genes.
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Acknowledgements
We thank K. Hussain and R. Hendriks for technical assistance and M. von Lindern for I/11 cells. This work is supported by The Netherlands Organisation for Scientific Research to W.d.L. as part of the Innovational Research Incentives Scheme and by grants from The Netherlands Organisation for Scientific Research and European Community to F.G.
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- Robert-Jan Palstra and Bas Tolhuis: These authors contributed equally to this work.
Authors and Affiliations
- Department of Cell Biology and Genetics, ErasmusMC, PO Box 1738, Rotterdam, 3000 DR, The Netherlands
Robert-Jan Palstra, Bas Tolhuis, Erik Splinter, Rian Nijmeijer, Frank Grosveld & Wouter de Laat
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Correspondence toWouter de Laat.
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Palstra, RJ., Tolhuis, B., Splinter, E. et al. The β-globin nuclear compartment in development and erythroid differentiation.Nat Genet 35, 190–194 (2003). https://doi.org/10.1038/ng1244
- Received: 01 August 2003
- Accepted: 02 September 2003
- Published: 21 September 2003
- Issue Date: 01 October 2003
- DOI: https://doi.org/10.1038/ng1244