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PMID: 8065342 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element.

Molecular and cellular biology ·Vol. 14 ·No. 9 ·1994-09-00 ·Pages 6087-96

Li Q, Stamatoyannopoulos JA

Abstract

We have analyzed the expression of human gamma-globin genes during development in F2 progeny of transgenic mice carrying two types of constructs. In the first type, gamma-globin genes were linked individually to large (approximately 4-kb) sequence fragments spanning locus control region (LCR) hypersensitive site 2 (HS2) or HS3. These LCR fragments contained not only the core HS elements but also extensive evolutionarily conserved flanking sequences. The second type of construct contained tandem gamma- and beta-globin genes linked to identical HS2 or HS3 fragments. We show that gamma-globin expression in transgenic mice carrying HS2 gamma or HS3 gamma constructs is highly sensitive to position effects and that such effects override the cis regulatory elements present in these constructs to produce markedly different developmental patterns of gamma-globin expression in lines carrying the same transgene. In contrast, gamma-globin expression in both HS2 gamma beta and HS3 gamma beta mice is sheltered from position effects and the developmental patterns of gamma-globin expression in lines carrying the same transgene are identical and display stage-specific regulation. The results suggest that cis regulatory sequences required for proper developmental control of fetal globin expression in the presence of an LCR element reside downstream from the gamma genes.

MeSH Terms
Age Factors Animals Gene Expression Regulation Globins/genetics Humans Mice Mice, Transgenic RNA, Messenger/genetics Regulatory Sequences, Nucleic Acid Transcription, Genetic
Chemicals
RNA, Messenger Globins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li Q
Division of Medical Genetics, School of Medicine, University of Washington, Seattle 98195.
Stamatoyannopoulos J A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.9.6087-6096.1994
Published
1994-09-00
Pages
6087-96
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359135
Subset
IM
Grants
NIDDK NIH HHS · DK 45365 · United States
NHLBI NIH HHS · HL 20899 · United States
External Links
PubMed source DOI: 10.1128/mcb.14.9.6087-6096.1994 PMC Full Text View journal details
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