Publication: Reactivation of a developmentally silenced embryonic globin gene
Issued Date
2021-12-01
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ISSN
20411723
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2-s2.0-85110947872
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.12, No.1 (2021)
Suggested Citation
Andrew J. King, Duantida Songdej, Damien J. Downes, Robert A. Beagrie, Siyu Liu, Megan Buckley, Peng Hua, Maria C. Suciu, A. Marieke Oudelaar, Lars L.P. Hanssen, Danuta Jeziorska, Nigel Roberts, Stephanie J. Carpenter, Helena Francis, Jelena Telenius, Aude Anais Olijnik, Jacqueline A. Sharpe, Jacqueline Sloane-Stanley, Jennifer Eglinton, Mira T. Kassouf, Stuart H. Orkin, Len A. Pennacchio, James O.J. Davies, Jim R. Hughes, Douglas R. Higgs, Christian Babbs Reactivation of a developmentally silenced embryonic globin gene. Nature Communications. Vol.12, No.1 (2021). doi:10.1038/s41467-021-24402-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/75927
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Title
Reactivation of a developmentally silenced embryonic globin gene
Author(s)
Andrew J. King
Duantida Songdej
Damien J. Downes
Robert A. Beagrie
Siyu Liu
Megan Buckley
Peng Hua
Maria C. Suciu
A. Marieke Oudelaar
Lars L.P. Hanssen
Danuta Jeziorska
Nigel Roberts
Stephanie J. Carpenter
Helena Francis
Jelena Telenius
Aude Anais Olijnik
Jacqueline A. Sharpe
Jacqueline Sloane-Stanley
Jennifer Eglinton
Mira T. Kassouf
Stuart H. Orkin
Len A. Pennacchio
James O.J. Davies
Jim R. Hughes
Douglas R. Higgs
Christian Babbs
Duantida Songdej
Damien J. Downes
Robert A. Beagrie
Siyu Liu
Megan Buckley
Peng Hua
Maria C. Suciu
A. Marieke Oudelaar
Lars L.P. Hanssen
Danuta Jeziorska
Nigel Roberts
Stephanie J. Carpenter
Helena Francis
Jelena Telenius
Aude Anais Olijnik
Jacqueline A. Sharpe
Jacqueline Sloane-Stanley
Jennifer Eglinton
Mira T. Kassouf
Stuart H. Orkin
Len A. Pennacchio
James O.J. Davies
Jim R. Hughes
Douglas R. Higgs
Christian Babbs
Abstract
The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues.