The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult β-like globin gene domains were evaluated in ≥90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-week gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic ε chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult β chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic → fetal and fetal → adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-α gene cluster, thus leading to a 5' → 3' activation of globin genes in a balanced fashion.

Molecular mechanisms of human hemoglobin switching: Selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts / Mavilio, F.; Giampaolo, A.; Care, A.; Migliaccio, G.; Calandrini, M.; Russo, G.; Pagliardi, G. L.; Mastroberardino, G.; Marinucci, M.; Peschle, C.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 80:22 I(1983), pp. 6907-6911. [10.1073/pnas.80.22.6907]

Molecular mechanisms of human hemoglobin switching: Selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts

Mavilio F.;
1983

Abstract

The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult β-like globin gene domains were evaluated in ≥90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-week gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic ε chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult β chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic → fetal and fetal → adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-α gene cluster, thus leading to a 5' → 3' activation of globin genes in a balanced fashion.
1983
80
6907
6911
Mavilio, F.; Giampaolo, A.; Care, A.; Migliaccio, G.; Calandrini, M.; Russo, G.; Pagliardi, G. L.; Mastroberardino, G.; Marinucci, M.; Peschle, C....espandi
Molecular mechanisms of human hemoglobin switching: Selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts / Mavilio, F.; Giampaolo, A.; Care, A.; Migliaccio, G.; Calandrini, M.; Russo, G.; Pagliardi, G. L.; Mastroberardino, G.; Marinucci, M.; Peschle, C.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 80:22 I(1983), pp. 6907-6911. [10.1073/pnas.80.22.6907]
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1237369
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 102
  • ???jsp.display-item.citation.isi??? 126
social impact