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PMID: 9742116 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The locus control region is necessary for gene expression in the human beta-globin locus but not the maintenance of an open chromatin structure in erythroid cells.

Molecular and cellular biology ·Vol. 18 ·No. 10 ·1998-10-00 ·Pages 5992-6000

Reik A, Telling A, Zitnik G, Cimbora D, Epner E, Groudine M

Abstract

Studies in many systems have led to the model that the human beta-globin locus control region (LCR) regulates the transcription, chromatin structure, and replication properties of the beta-globin locus. However the precise mechanisms of this regulation are unknown. We have developed strategies to use homologous recombination in a tissue culture system to examine how the LCR regulates the locus in its natural chromosomal environment. Our results show that when the functional components of the LCR, as defined by transfection and transgenic studies, are deleted from the endogenous beta-globin locus in an erythroid background, transcription of all beta-globin genes is abolished in every cell. However, formation of the remaining hypersensitive site(s) of the LCR and the presence of a DNase I-sensitive structure of the beta-globin locus are not affected by the deletion. In contrast, deletion of 5'HS5 of the LCR, which has been suggested to serve as an insulator, has only a minor effect on beta-globin transcription and does not influence the chromatin structure of the locus. These results show that the LCR as currently defined is not necessary to keep the locus in an "open" conformation in erythroid cells and that even in an erythroid environment an open locus is not sufficient to permit transcription of the beta-like globin genes.

MeSH Terms
Adult Animals Cell Line Chickens Chromatin Erythroid Precursor Cells Gene Expression Regulation Globins/genetics Humans Locus Control Region
Chemicals
Chromatin Globins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Reik A
Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Telling A
Zitnik G
Cimbora D
Epner E
Groudine M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.10.5992
Published
1998-10-00
Pages
5992-6000
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109185
Subset
IM
Grants
NCI NIH HHS · CA54337 · United States
NIDDK NIH HHS · DK44746 · United States
NIDDK NIH HHS · DK52854 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.10.5992 PMC Full Text View journal details
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