Molecular analysis of the human. beta. -globin locus activation region

Journal Article · Sat Jul 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.14.5439· OSTI ID:5300040

Forrester, W C; Novak, U; Gelinas, R; Groudine, M ^[1]

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1. Fred Hutchinson Cancer Research Center, Seattle, WA (USA)

Recently, DNA sequences containing four erythroid-specific DNase I hypersensitive sites within 20 kilobases 5{prime} of the human {epsilon}-globin gene have been identified as an important cis-acting regulatory element, the locus activation region (LAR). Subfragments of the LAR, containing either all or only the two 5{prime} or two 3{prime} hypersensitive sites were linked to the human {beta}-globin gene and analyzed for their effect on globin gene expression in stably transformed mouse erythroleukemia (MEL) cells. Constructs containing all four of the hypersensitive sites increase {beta}-gobin mRNA levels 8- to 13-fold, while constructs with only the 5{prime} or 3{prime} sites increase globin expression to a lesser extent. No effect was seen when the constructs were assayed in 3T3 fibroblasts. All of the LAR derivatives form hypersensitive sites at the corresponding sequence position in MEL cells prior to and after induction of MEL cell differentiation. However, in 3T3 fibroblasts only the hypersensitive site corresponding to the previously described erythroid-specific {minus}10.9 site was formed.

• OSTI ID: 5300040
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:14; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
CELL CONSTITUENTS
CHROMATIN
CONNECTIVE TISSUE CELLS
DNA
DNA-ASE
ELECTROPHORESIS
ENZYMES
ESTERASES
FIBROBLASTS
GENE REGULATION
GENES
GLOBIN
HYDROLASES
MAMMALS
MAN
MESSENGER-RNA
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
PLASMIDS
PRIMATES
RNA
SOMATIC CELLS
VERTEBRATES