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PMID: 12861010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus.

Molecular and cellular biology ·Vol. 23 ·No. 15 ·2003-08-00 ·Pages 5234-44

Bulger M, Schübeler D, Bender MA, Hamilton J, Farrell CM, Hardison RC, Groudine M

Abstract

In order to create an extended map of chromatin features within a mammalian multigene locus, we have determined the extent of nuclease sensitivity and the pattern of histone modifications associated with the mouse beta-globin genes in adult erythroid tissue. We show that the nuclease-sensitive domain encompasses the beta-globin genes along with several flanking olfactory receptor genes that are inactive in erythroid cells. We describe enhancer-blocking or boundary elements on either side of the locus that are bound in vivo by the transcription factor CTCF, but we found that they do not coincide with transitions in nuclease sensitivity flanking the locus or with patterns of histone modifications within it. In addition, histone hyperacetylation and dimethylation of histone H3 K4 are not uniform features of the nuclease-sensitive mouse beta-globin domain but rather define distinct subdomains within it. Our results reveal a complex chromatin landscape for the active beta-globin locus and illustrate the complexity of broad structural changes that accompany gene activation.

MeSH Terms
Animals Base Sequence Binding Sites Blotting, Southern CCCTC-Binding Factor Cell Nucleus/metabolism Chickens Chromatin/metabolism DNA-Binding Proteins/metabolism Deoxyribonucleases/metabolism Erythrocytes/metabolism Globins/genetics,metabolism Histones/metabolism Humans K562 Cells Mice Models, Genetic Molecular Sequence Data Precipitin Tests Protein Structure, Tertiary Repressor Proteins Spleen/metabolism Transcription Factors/metabolism
Chemicals
CCCTC-Binding Factor CTCF protein, human Chromatin Ctcf protein, mouse DNA-Binding Proteins Histones Repressor Proteins Transcription Factors Globins Deoxyribonucleases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bulger Michael
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Schübeler Dirk
Bender M A
Hamilton Joan
Farrell Catherine M
Hardison Ross C
Groudine Mark
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.15.5234-5244.2003
Published
2003-08-00
Pages
5234-44
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC165715
Subset
IM
Grants
NIDDK NIH HHS · DK 44746 · United States
NHGRI NIH HHS · HG 02238 · United States
NIDDK NIH HHS · R37 DK044746 · United States
NIDDK NIH HHS · DK 27635 · United States
NHLBI NIH HHS · HL 57620 · United States
NHGRI NIH HHS · R01 HG002238 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.15.5234-5244.2003 PMC Full Text View journal details
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