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PMID: 9207043 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Analysis of enhancer function of the HS-40 core sequence of the human alpha-globin cluster.

Nucleic acids research ·Vol. 25 ·No. 14 ·1997-07-15 ·Pages 2917-22

Chen H, Lowrey CH, Stamatoyannopoulos G

Abstract

HS-40 is the major regulatory element of the human alpha-globin locus, located 40 kb upstream of the zeta-globin gene. To test for potential interactions between HS-40 and the beta- or the gamma-globin gene promoters in stable transfection assays, the HS-40 core sequence was cloned upstream of either the beta promoter or the gamma promoter driving the neomycin phosphotransferase gene and enhancer activity was measured using a colony assay. In K562 or in MEL cells, enhancer activity of HS-40 was higher than that of the individual core sequences of the DNase I hypersensitive sites (HS) of the beta-globin locus control region (LCR), and approximately 60% of the enhancer activity of a 2.5 kb microLCR, which contains the core elements of DNase I hypersensitive sites 1-4. In contrast to the synergistic interaction between the DNase I hypersensitive sites of beta locus LCR, combination of HS-40 with these DNase I hypersensitive sites failed to display cooperativity in K562 cells and inhibited enhancer function in MEL cells. Inhibition of enhancer function was also observed when two copies of the HS-40 were arranged tandemly. We conclude that the core element of HS-40 (i) is a powerful enhancer of gamma- and beta-globin gene expression, (ii) in contrast to other classical enhancers, acts best as a single copy, (iii) does not cooperate with the regulatory elements of the beta-globin locus control region.

MeSH Terms
Animals Binding Sites Deoxyribonuclease I Enhancer Elements, Genetic Globins/genetics Humans Mice Multigene Family Promoter Regions, Genetic Repetitive Sequences, Nucleic Acid Tumor Cells, Cultured
Chemicals
Globins Deoxyribonuclease I
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen H
Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, Seattle, WA 98195-7720, USA.
Lowrey C H
Stamatoyannopoulos G
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/25.14.2917
Published
1997-07-15
Pages
2917-22
Language
English
Region
England
NLM ID
0411011
PMCID
PMC146810
Subset
IM
Grants
NIDDK NIH HHS · DK45365 · United States
NHLBI NIH HHS · HL53750 · United States
NHLBI NIH HHS · R01 HL52243 · United States
External Links
PubMed source DOI: 10.1093/nar/25.14.2917 PMC Full Text View journal details
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