Dual role for the methyltransferase G9a in the maintenance of beta-globin gene transcription in adult erythroid cells

作者：Chaturvedi Chandra Prakash; Hosey Alison M; Palii Carmen; Perez Iratxeta Carolina; Nakatani Yoshihiro; Ranish Jeffrey A; Dilworth F Jeffrey; Brand Marjorie^*

来源：Proceedings of the National Academy of Sciences, 2009, 106(43): 18303-18308.

DOI：10.1073/pnas.0906769106

• chromatin
• histone methylation
• UTX
• NF-E2

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.

• 出版日期2009-10-27