TY - JOUR
T1 - A deletion of the human β-globin locus activation region causes a major alteration in chromatin structure and replication across the entire β-globin locus
AU - Forrester, William C.
AU - Epner, Elliot
AU - Catherine Driscoll, M.
AU - Enver, Tariq
AU - Brice, Martha
AU - Papayannopoulou, Thalia
AU - Groudine, Mark
PY - 1990
Y1 - 1990
N2 - Naturally occurring deletions that remove sequences located ∼60 kb upstream of the human adult β-globin gene result in the failure to transcriptionally activate the cis-linked globin genes in erythroid cells. In addition, transfection, transgenic, and somatic cell hybrid studies have revealed that sequences within this region are essential for the developmentally regulated high-level expression of cis-linked globin genes. This regulatory region located at the 5′ end of the β-globin locus has been termed the locus activation region (LAR). Using somatic cell hybrids, we have studied the chromatin structure and timing of DNA replication of the normal human β-globin locus and a locus containing a de novo 25-kb deletion that removes elements of the LAR. As a result of this deletion, the entire β-globin locus and sequences ∼100 kb 5′ and 3′ of the adult β-globin gene are DNase I-resistant and do not form characteristic distant hypersensitive sites. These sequences also replicate late in S phase in an erythroid cell background. In contrast, the sequences of the normal locus are DNase I sensitive and early replicating. These results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance.
AB - Naturally occurring deletions that remove sequences located ∼60 kb upstream of the human adult β-globin gene result in the failure to transcriptionally activate the cis-linked globin genes in erythroid cells. In addition, transfection, transgenic, and somatic cell hybrid studies have revealed that sequences within this region are essential for the developmentally regulated high-level expression of cis-linked globin genes. This regulatory region located at the 5′ end of the β-globin locus has been termed the locus activation region (LAR). Using somatic cell hybrids, we have studied the chromatin structure and timing of DNA replication of the normal human β-globin locus and a locus containing a de novo 25-kb deletion that removes elements of the LAR. As a result of this deletion, the entire β-globin locus and sequences ∼100 kb 5′ and 3′ of the adult β-globin gene are DNase I-resistant and do not form characteristic distant hypersensitive sites. These sequences also replicate late in S phase in an erythroid cell background. In contrast, the sequences of the normal locus are DNase I sensitive and early replicating. These results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance.
KW - Locus activation region
KW - β-Globin gene
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U2 - 10.1101/gad.4.10.1637
DO - 10.1101/gad.4.10.1637
M3 - Article
C2 - 2249769
AN - SCOPUS:0025107556
SN - 0890-9369
VL - 4
SP - 1637
EP - 1649
JO - Genes and Development
JF - Genes and Development
IS - 10
ER -