Nature Communications (Jul 2021)
Reactivation of a developmentally silenced embryonic globin gene
- 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
Affiliations
- Andrew J. King
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Duantida Songdej
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Damien J. Downes
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Robert A. Beagrie
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Siyu Liu
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Megan Buckley
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Peng Hua
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Maria C. Suciu
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- A. Marieke Oudelaar
- Max Planck Institute for Biophysical Chemistry
- Lars L. P. Hanssen
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Danuta Jeziorska
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Nigel Roberts
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Stephanie J. Carpenter
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Helena Francis
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Jelena Telenius
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Aude-Anais Olijnik
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Jacqueline A. Sharpe
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Jacqueline Sloane-Stanley
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Jennifer Eglinton
- National Haemoglobinopathy Reference Laboratory, Department of Haematology, Level 4, John Radcliffe Hospital
- Mira T. Kassouf
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Stuart H. Orkin
- Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School and Howard Hughes Medical Institute
- Len A. Pennacchio
- Functional Genomics Department, Lawrence Berkeley National Laboratory
- James O. J. Davies
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Jim R. Hughes
- MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Douglas R. Higgs
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Christian Babbs
- MRC Weatherall Institute of Molecular Medicine, University of Oxford
- DOI
- https://doi.org/10.1038/s41467-021-24402-3
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 15
Abstract
Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.