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PMID: 11593024 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a conserved erythroid specific domain of histone acetylation across the alpha-globin gene cluster.

Anguita E, Johnson CA, Wood WG, Turner BM, Higgs DR

Abstract

We have analyzed the pattern of core histone acetylation across 250 kb of the telomeric region of the short arm of human chromosome 16. This gene-dense region, which includes the alpha-globin genes and their regulatory elements embedded within widely expressed genes, shows marked differences in histone acetylation between erythroid and non-erythroid cells. In non-erythroid cells, there was a uniform 2- to 3-fold enrichment of acetylated histones, compared with heterochromatin, across the entire region. In erythroid cells, an approximately 100-kb segment of chromatin encompassing the alpha genes and their remote major regulatory element was highly enriched in histone H4 acetylated at Lys-5. Other lysines in the N-terminal tail of histone H4 showed intermediate and variable levels of enrichment. Similar broad segments of erythroid-specific histone acetylation were found in the corresponding syntenic regions containing the mouse and chicken alpha-globin gene clusters. The borders of these regions of acetylation are located in similar positions in all three species, and a sharply defined 3' boundary coincides with the previously identified breakpoint in conserved synteny between these species. We have therefore demonstrated that an erythroid-specific domain of acetylation has been conserved across several species, encompassing not only the alpha-globin genes but also a neighboring widely expressed gene. These results contrast with those at other clusters and demonstrate that not all genes are organized into discrete regulatory domains.

MeSH Terms
Acetylation Animals Binding Sites Cell Line, Transformed Chickens Chromosomes, Human, Pair 16 Conserved Sequence Erythrocytes Globins/genetics Histones/metabolism Humans K562 Cells Mice Multigene Family Synteny Tumor Cells, Cultured
Chemicals
Histones Globins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Anguita E
Medical Research Council Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Johnson C A
Wood W G
Turner B M
Higgs D R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2001-10-09
Epub
2001-00-02
Pages
12114-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC59777
Subset
IM
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