Dual role for the methyltransferase G9a in the maintenance of beta-globin gene transcription in adult erythroid cells.
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.
Chaturvedi
Chandra-Prakash
CP
The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada.
Hosey
Alison M
AM
Palii
Carmen
C
Perez-Iratxeta
Carolina
C
Nakatani
Yoshihiro
Y
Ranish
Jeffrey A
JA
Dilworth
F Jeffrey
FJ
Brand
Marjorie
M
D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000378:metabolism; D011485:Protein Binding; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics*
D006657:Histones; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D055544:beta-Globins; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase