Dataset Information

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.

SUBMITTER: Chaturvedi CP

PROVIDER: S-EPMC2775297 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chaturvedi Chandra-Prakash CP 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

Proceedings of the National Academy of Sciences of the United States of America 20091012 43

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 ...[more]

PMID: 19822740

Similar Datasets

Project description:UNLABELLED: BACKGROUND: The ?-globin gene domains of vertebrate animals constitute popular models for studying the regulation of eukaryotic gene transcription. It has previously been shown that in the mouse the developmental switching of globin gene expression correlates with the reconfiguration of an active chromatin hub (ACH), a complex of promoters of transcribed genes with distant regulatory elements. Although it is likely that observations made in the mouse ?-globin gene domain are also relevant for this locus in other species, the validity of this supposition still lacks direct experimental evidence. Here, we have studied the spatial organization of the chicken ?-globin gene domain. This domain is of particular interest because it represents the perfect example of the so-called 'strong' tissue-specific gene domain flanked by insulators, which delimit the area of preferential sensitivity to DNase I in erythroid cells. RESULTS: Using chromosome conformation capture (3C), we have compared the spatial configuration of the ?-globin gene domain in chicken red blood cells (RBCs) expressing embryonic (3-day-old RBCs) and adult (9-day-old RBCs) ?-globin genes. In contrast to observations made in the mouse model, we found that in the chicken, the early embryonic ?-globin gene, ?, did not interact with the locus control region in RBCs of embryonic lineage (3-day RBCs), where this gene is actively transcribed. In contrast to the mouse model, a strong interaction of the promoter of another embryonic ?-globin gene, ?, with the promoter of the adult ?-globin gene, ?A, was observed in RBCs from both 3-day and 9-day chicken embryos. Finally, we have demonstrated that insulators flanking the chicken ?-globin gene domain from the upstream and from the downstream interact with each other, which places the area characterized by lineage-specific sensitivity to DNase I in a separate chromatin loop. CONCLUSIONS: Taken together, our results strongly support the ACH model but show that within a domain of tissue-specific genes, the active status of a promoter does not necessarily correlate with the recruitment of this promoter to the ACH.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets