Identification of a conserved erythroid specific domain of histone acetylation across the α-globin gene cluster
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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 α-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 ≈100-kb segment of chromatin encompassing the α 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 α-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 α-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.
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Activation of α-globin expression in erythroid cells is associated with the appearance of a broad domain of histone acetylation and H3K4me1 spanning ~80kb including the α-globin genes and their regulatory elements.
“activation of α-globin expression in erythroid cells is associated with the appearance of a broad domain of histone acetylation and modification by H3K4me1 spanning ~80kb including the α-globin genes and their regulatory elements (Fig. 1B)13,14.”
From Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo (2017) · cites this paper as [13]
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Self-citation
- Authors
- Anguita, E., Johnson, C. A., Wood, W. G., Turner, B. M., & Higgs, D. R.
- Affiliations
- John Radcliffe Hospital (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-10-02
- Volume
- 98
- Issue
- 21
- Pages
- 12114-12119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC59777
- OpenAlex
- W2067137429
- Cited by
- 70
- References
- 51
- Citations by year
- 2021: 1 · 2019: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- histone acetylation, alpha-globin gene cluster, heterochromatin, synteny conservation, chromatin organization
- MeSH terms
- Acetylation, Animals, Binding Sites, Cell Line, Transformed, Chickens, Chromosomes, Human, Pair 16, Erythrocytes, Multigene Family, Globins, Histones, Humans, Tumor Cells, Cultured, Conserved Sequence, K562 Cells, Synteny, Mice
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