Histone acetylation at the human beta-globin locus changes with developmental age.
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 chromatin immunoprecipitation (ChIP) assays. Using this common standard, we found that the locus control region (LCR) was acetylated to the same level at all stages, whereas acetylation levels at the individual gene regions correlated with the state of transcription. In the active genes, the promoters were less acetylated compared with 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. Although 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.
Yin
Wenxuan
W
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, 98195, USA.
Barkess
Gráinne
G
Fang
Xiangdong
X
Xiang
Ping
P
Cao
Hua
H
Stamatoyannopoulos
George
G
Li
Qiliang
Q
D000107:Acetylation; D000328:Adult; D000375:Aging / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004257:DNA Polymerase II / Q000378:metabolism; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019901:Locus Control Region / Q000502:physiology*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D040641:Quantitative Trait Loci / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D006657:Histones; D009707:Nucleosomes; D005914:Globins; D004257:DNA Polymerase II