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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4101-4107.
Prepublished online as a Blood First Edition Paper on September 19, 2007; DOI 10.1182/blood-2007-05-091256.


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Submitted May 17, 2007
Accepted September 11, 2007

Histone acetylation at the human {beta}-globin locus changes with developmental age

Wenxuan Yin, Grainne Barkess, Xiangdong Fang, Ping Xiang, Hua Cao, George Stamatoyannopoulos, and Qiliang Li*

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States

* Corresponding author; email: li111640{at}u.washington.edu.

To delineate the relationship between epigenetic modifications and hemoglobin switching we compared the pattern of histone acetylation and pol II binding across the {beta}-globin locus at fetal and adult stages of human development. To make this comparison possible, we introduced an external control into experimental samples in ChIP assays. By using this common standard we found that the LCR was acetylated to the same level at all stages, while acetylation levels at the individual gene regions correlated with the state of transcription. In the active genes the promoters were less acetylated compared to the coding regions. Furthermore, all globin promoters were acetylated to a similar level irrespective of the state of transcription. However, after correction for the loss of nucleosomes, the level of acetylation per histone at the active {gamma} and {beta} promoters was 5 to 7 fold greater than that at the inactive {epsilon} promoter. While the histone acetylation level within the LCR was developmentally stable, pol II binding in fetal erythroblasts was 2 to 3 fold greater than that in adult erythroblasts. These results demonstrate that dynamic changes in histone acetylation and pol II take place as the human {beta}-globin gene region undergoes its developmental switches.


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