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PMID: 9632803 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion.

Molecular and cellular biology ·Vol. 18 ·No. 7 ·1998-07-00 ·Pages 4188-96

Navas PA, Peterson KR, Li Q, Skarpidi E, Rohde A, Shaw SE, Clegg CH, Asano H, Stamatoyannopoulos G

Abstract

The human beta-globin locus control region (LCR) consists of five erythroid-lineage-specific DNase I-hypersensitive sites (HSs) and is required for activation of the beta-globin locus chromatin domain and globin gene expression. Each DNase I-HS of the LCR consists of a highly conserved core element and flanking sequences. To analyze the functional role of the core elements of the HSs, we deleted a 234-bp fragment encompassing the core of HS3 (HS3c) from a beta-globin locus residing on a 248-kb beta-locus yeast artificial chromosome and analyzed its function in F2 progeny of transgenic mice. Human epsilon-globin gene expression was absent at day 10 and severely reduced in the day 12 embryonic erythropoiesis of mice lacking HS3c. In contrast, gamma-globin gene expression was normal in embryonic erythropoiesis but it was absent in definitive erythropoiesis in the fetal liver. These results indicate that the core element of HS3 is necessary for epsilon-globin gene transcription in embryonic cells and for gamma-globin gene transcription in definitive cells. Normal gamma-globin gene expression in embryonic cells and the absence of gamma-globin gene expression in definitive cells show that different HSs interact with gamma-globin gene promoters in these two stages of development. Such results provide direct evidence for developmental stage specificity of the interactions between the core elements of HSs and the promoters of the globin genes.

MeSH Terms
Animals Chromosomes, Artificial, Yeast Erythroid Precursor Cells Erythropoiesis Gene Expression Regulation, Developmental Globins/genetics Humans Locus Control Region Mice Mice, Transgenic
Chemicals
Globins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Navas P A
Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA.
Peterson K R
Li Q
Skarpidi E
Rohde A
Shaw S E
Clegg C H
Asano H
Stamatoyannopoulos G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.7.4188
Published
1998-07-00
Pages
4188-96
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109003
Subset
IM
Grants
NHLBI NIH HHS · HL20899 · United States
NHLBI NIH HHS · HL53750 · United States
NIDDK NIH HHS · DK45365 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.7.4188 PMC Full Text View journal details
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