Dataset Information

CpG hypomethylation in a large domain encompassing the embryonic beta-like globin genes in primitive erythrocytes.

ABSTRACT: There is little evidence addressing the role of CpG methylation in transcriptional control of genes that do not contain CpG islands. This is reflected in the ongoing debate about whether CpG methylation merely suppresses retroelements or if it also plays a role in developmental and tissue-specific gene regulation. The genes of the beta-globin locus are an important model of mammalian developmental gene regulation and do not contain CpG islands. We have analyzed the methylation status of regions in the murine beta-like globin locus in uncultured primitive and definitive erythroblasts and other cultured primary and transformed cell types. A large ( approximately 20-kb) domain is hypomethylated only in primitive erythroid cells; it extends from the region just past the locus control region to before beta-major and encompasses the embryonic genes Ey, beta h1, and beta h0. Even retrotransposons in this region are hypomethylated in primitive erythroid cells. The existence of this large developmentally regulated domain of hypomethylation supports a mechanistic role for DNA methylation in developmental regulation of globin genes.

SUBMITTER: Hsu M

PROVIDER: S-EPMC1951500 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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CpG hypomethylation in a large domain encompassing the embryonic beta-like globin genes in primitive erythrocytes.

Hsu Mei M Mabaera Rodwell R Lowrey Christopher H CH Martin David I K DI Fiering Steven S

Molecular and cellular biology 20070423 13

There is little evidence addressing the role of CpG methylation in transcriptional control of genes that do not contain CpG islands. This is reflected in the ongoing debate about whether CpG methylation merely suppresses retroelements or if it also plays a role in developmental and tissue-specific gene regulation. The genes of the beta-globin locus are an important model of mammalian developmental gene regulation and do not contain CpG islands. We have analyzed the methylation status of regions ...[more]

PMID: 17452448

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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

CpG hypomethylation in a large domain encompassing the embryonic beta-like globin genes in primitive erythrocytes.

Publications

CpG hypomethylation in a large domain encompassing the embryonic beta-like globin genes in primitive erythrocytes.

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