Dual role for the methyltransferase G9a in the maintenance of β-globin gene transcription in adult erythroid cells
- Chandra-Prakash Chaturvedia,1,
- Alison M. Hoseya,1,
- Carmen Paliia,
- Carolina Perez-Iratxetaa,
- Yoshihiro Nakatanib,
- Jeffrey A. Ranishc,
- F. Jeffrey Dilwortha,d and
- Marjorie Branda,d,2
- aThe Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada K1H 8L6;
- bDana-Farber Cancer Institute, Boston, MA 02115;
- cInstitute for Systems Biology, Seattle, WA 98103; and
- dDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6
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↵1C.-P.C. and A.M.H. contributed equally to this work.
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Edited by Mark T. Groudine, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved September 4, 2009 (received for review June 16, 2009)
Abstract
Using a proteomics screen, we have identified the methyltransferase G9a as an interacting partner of the hematopoietic activator NF-E2. We show that G9a is recruited to the β-globin locus in a NF-E2-dependent manner and spreads over the entire locus. While G9a is often regarded as a corepressor, knocking down this protein in differentiating adult erythroid cells leads to repression of the adult βmajglobin gene and aberrant reactivation of the embryonic β-like globin gene Ey. While in adult cells G9a maintains Ey in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates βmaj transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the βmaj (but not the Ey) promoter where it antagonizes G9a-dependent H3K27 dimethylation. Collectively, these results reveal a dual role for G9a in maintaining proper expression (both repression and activation) of the β-globin genes in differentiating adult erythroid cells.
Footnotes
- 2To whom correspondence should be addressed. E-mail: mbrand{at}ohri.ca
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Author contributions: C.-P.C., A.M.H., F.J.D., and M.B. designed research; C.-P.C., A.M.H., C.P., J.A.R., and M.B. performed research; Y.N. and F.J.D. contributed new reagents/analytic tools; C.-P.C., A.M.H., C.P.-I., J.A.R., and M.B. analyzed data; and M.B. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
