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

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 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 E(y)) 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.

authors

Chaturvedi CP,Hosey AM,Palii C,Perez-Iratxeta C,Nakatani Y,Ranish JA,Dilworth FJ,Brand M

doi

10.1073/pnas.0906769106

subject

Has Abstract

pub_date

2009-10-27 00:00:00

pages

18303-8

issue

43

eissn

0027-8424

issn

1091-6490

pii

0906769106

journal_volume

106

pub_type

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