This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harju, S. Articles by Peterson, K. R. Search for Related Content PubMed PubMed Citation Articles by Harju, S. Articles by Peterson, K. R.

Next Article 

Molecular and Cellular Biology, October 2005, p. 8765-8778, Vol. 25, No. 20
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.20.8765-8778.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Genome Architecture of the Human ß-Globin Locus Affects Developmental Regulation of Gene Expression

Susanna Harju,¹ Patrick A. Navas,² George Stamatoyannopoulos,² and Kenneth R. Peterson^1,3*

Department of Biochemistry and Molecular Biology,¹ Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160,³ Division of Medical Genetics, University of Washington, Seattle, Washington 98195²

Received 16 January 2005/ Returned for modification 10 February 2005/ Accepted 21 July 2005

To test the role of gene order in globin gene expression, mutant human ß-globin locus yeast artificial chromosome constructs were used, each having one additional globin gene encoding a "marked" transcript (^m, ^m, or ß^m) integrated at different locations within the locus. When a ß^m-globin gene was placed between the locus control region (LCR) and the -globin gene, ß^m-globin expression dominated primitive and definitive erythropoiesis; only ß^m-globin mRNA was detected during the fetal and adult definitive stages of erythropoiesis. When an ^Am-globin gene was placed at the same location, ^Am-globin was expressed during embryonic erythropoiesis and the fetal liver stage of definitive erythropoiesis but was silenced during the adult stage. The downstream wild-type -globin genes were not expressed. When an ^m-globin gene was placed between the - and ß-globin genes, it remained silent during embryonic erythropoiesis; only the LCR-proximal wild-type -globin gene was expressed. Placement of a ß^m-globin gene upstream of the ^G-globin gene resulted in expression of ß^m-globin in embryonic cells and in a significant decrease in expression of the downstream wild-type ß-globin gene. These results indicate that distance from the LCR, an inherent property of spatial gene order, is a major determinant of temporal gene expression during development.

---

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, MS 3030, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160-7421. Phone: (913) 588-6907. Fax: (913) 588-7440. E-mail: kpeterson{at}kumc.edu.

Supplemental material for this article may be found at http://mcb.asm.org/.

---

Molecular and Cellular Biology, October 2005, p. 8765-8778, Vol. 25, No. 20
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.20.8765-8778.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Beauchemin, H., Trudel, M. (2009). Evidence for a Bigenic Chromatin Subdomain in Regulation of the Fetal-to-Adult Hemoglobin Switch. Mol. Cell. Biol. 29: 1635-1648 [Abstract] [Full Text]  
• Chen, Z., Luo, H.-Y., Basran, R. K., Hsu, T.-H., Mang, D. W. H., Nuntakarn, L., Rosenfield, C. G., Patrinos, G. P., Hardison, R. C., Steinberg, M. H., Chui, D. H. K. (2008). A T-to-G Transversion at Nucleotide -567 Upstream of HBG2 in a GATA-1 Binding Motif Is Associated with Elevated Hemoglobin F. Mol. Cell. Biol. 28: 4386-4393 [Abstract] [Full Text]  
• Harju-Baker, S., Costa, F. C., Fedosyuk, H., Neades, R., Peterson, K. R. (2008). Silencing of A{gamma}-Globin Gene Expression during Adult Definitive Erythropoiesis Mediated by GATA-1-FOG-1-Mi2 Complex Binding at the -566 GATA Site. Mol. Cell. Biol. 28: 3101-3113 [Abstract] [Full Text]  
• Thurman, R. E., Day, N., Noble, W. S., Stamatoyannopoulos, J. A. (2007). Identification of higher-order functional domains in the human ENCODE regions. Genome Res 17: 917-927 [Abstract] [Full Text]  
• Johnson, R. M., Prychitko, T., Gumucio, D., Wildman, D. E., Uddin, M., Goodman, M. (2006). Phylogenetic comparisons suggest that distance from the locus control region guides developmental expression of primate beta-type globin genes. Proc. Natl. Acad. Sci. USA 103: 3186-3191 [Abstract] [Full Text]