Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 43, Pages 18303-18308Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0906769106
Keywords
chromatin; histone methylation; UTX; NF-E2
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Funding
- Canadian Institutes of Health Research
- Terry Fox Foundation (Canadian Cancer Society Research Institute)
- CIHR/Thalassemia Foundation of Canada fellowship
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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 beta-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 beta(maj) globin gene and aberrant reactivation of the embryonic beta-like globin gene E-y. While in adult cells G9a maintains E-y in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates beta(maj) transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the beta(maj) (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 beta-globin genes in differentiating adult erythroid cells.
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