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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2210-2216.
Prepublished online as a Blood First Edition Paper on October 31, 2006; DOI 10.1182/blood-2006-06-029868.
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RED CELLS
Transcriptional interference among the murine ß-like globin genes
Xiao Hu1,
Susan Eszterhas1,
Nicolas Pallazzi2,
Eric E. Bouhassira2,
Jennifer Fields1,
Osamu Tanabe3,
Scott A. Gerber4,
Michael Bulger5,
James Douglas Engel3,
Mark Groudine6, and
Steven Fiering1,4
1 Department of Microbiology/Immunology and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH;
2 Department of Medicine, Division of Hematology, Albert Einstein College of Medicine, Bronx, NY;
3 Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor;
4 Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH;
5 Center for Human Genetics and Molecular Pediatric Disease and Department of Biophysics and Biochemistry, University of Rochester, NY;
6 Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Mammalian ß-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity. To investigate the influence of transcription by the murine embryonic genes on transcription of the other ß-like genes, we generated mice with deletions of the promoter regions of Ey and ßh1 and measured transcription of the remaining genes. Deletion of the Ey and ßh1 promoters increased transcription of ßmajor and ßminor 2-fold to 3-fold during primitive erythropoiesis. Deletion of Ey did not affect ßh1 nor did deletion of ßh1 affect Ey, but Ey deletion uniquely activated transcription from ßh0, a ß-like globin gene immediately downstream of Ey. Protein analysis showed that ßh0 encodes a translatable ß-like globin protein that can pair with alpha globin. The lack of transcriptional interference between Ey and ßh1 and the gene-specific repression of ßh0 did not support LCR competition among the embryonic genes and suggested that direct transcriptional interference from Ey suppressed ßh0.
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