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

William C. Forrester, Elliot Epner, M. Catherine Driscoll, Tariq Enver, Martha Brice, Thalia Papayannopoulou, Mark Groudine

Research output: Contribution to journalArticle

371 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1637-1649
Number of pages13
JournalGenes and Development
Volume4
Issue number10
StatePublished - 1990
Externally publishedYes

Fingerprint

Globins
Chromatin
DNA Replication Timing
Erythroid Cells
Hybrid Cells
Deoxyribonuclease I
Genes
Sequence Deletion
Nucleic Acid Regulatory Sequences
S Phase
Transfection

Keywords

  • β-Globin gene
  • Locus activation region

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Forrester, W. C., Epner, E., Catherine Driscoll, M., Enver, T., Brice, M., Papayannopoulou, T., & Groudine, M. (1990). 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. Genes and Development, 4(10), 1637-1649.

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. / Forrester, William C.; Epner, Elliot; Catherine Driscoll, M.; Enver, Tariq; Brice, Martha; Papayannopoulou, Thalia; Groudine, Mark.

In: Genes and Development, Vol. 4, No. 10, 1990, p. 1637-1649.

Research output: Contribution to journalArticle

Forrester, WC, Epner, E, Catherine Driscoll, M, Enver, T, Brice, M, Papayannopoulou, T & Groudine, M 1990, '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', Genes and Development, vol. 4, no. 10, pp. 1637-1649.
Forrester, William C. ; Epner, Elliot ; Catherine Driscoll, M. ; Enver, Tariq ; Brice, Martha ; Papayannopoulou, Thalia ; Groudine, Mark. / 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. In: Genes and Development. 1990 ; Vol. 4, No. 10. pp. 1637-1649.
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