A developmentally stable chromatin structure in the human beta-globin gene cluster.
The DNase I-hypersensitive sites in the human embryonic beta-globin gene region have been mapped in erythroid-enriched fractions of disaggregated fetal livers, in adult nucleated red blood cells, and in fetal brain tissue. Our analysis of a region extending 11 kilobases (kb) 5' of the epsilon-globin gene reveals many minor nuclease-hypersensitive sites and one major site located 6.1 kb upstream of the epsilon-globin gene. All of these hypersensitive sites are erythroid-specific, and the major site is stable throughout erythroid development. As assayed by nuclear runoff transcription, little or no epsilon-globin gene expression is detectable in fetal or adult erythroid cells. Thus, the presence of the major hypersensitive site 5' of the epsilon-globin gene in both fetal and adult erythroid cells demonstrates that this site is not specifically correlated with transcription of the gene or with a particular stage of development. Rather, this site may reflect an early event in erythroid differentiation. In addition, DNase I has been used to probe the overall sensitivity of epsilon-globin chromatin in fetal erythroid cells. Our findings indicate that the epsilon-globin gene as well as the other genes in the beta-globin cluster reside within the chromatin domain that is more DNase I-sensitive than "bulk" chromatin.
Forrester
W C
WC
Thompson
C
C
Elder
J T
JT
Groudine
M
M
D001921:Brain / Q000196:embryology; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004900:Erythroblasts / Q000502:physiology / Q000648:ultrastructure; D004920:Erythropoiesis; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000196:embryology; D014018:Tissue Distribution; D014158:Transcription, Genetic
D002843:Chromatin; D005914:Globins; D003850:Deoxyribonuclease I