This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prioleau, M.-N. Articles by Hyrien, O. Search for Related Content PubMed PubMed Citation Articles by Prioleau, M.-N. Articles by Hyrien, O.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2003, p. 3536-3549, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3536-3549.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Replication of the Chicken ß-Globin Locus: Early-Firing Origins at the 5' HS4 Insulator and the - and ß^A-Globin Genes Show Opposite Epigenetic Modifications

Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, 75230 Paris Cedex 05,¹ Institut Jacques Monod, 75005 Paris, France²

Received 12 December 2002/ Returned for modification 15 January 2003/ Accepted 4 March 2003

Chromatin structure is believed to exert a strong effect on replication origin function. We have studied the replication of the chicken ß-globin locus, whose chromatin structure has been extensively characterized. This locus is delimited by hypersensitive sites (HSs) that mark the position of insulator elements. A stretch of condensed chromatin and another HS separate the ß-globin domain from an adjacent folate receptor (FR) gene. We demonstrate here that in erythroid cells that express the FR but not the globin genes, replication initiates at four sites within the ß-globin domain, one at the 5' HS4 insulator and the other three near the - and ß^A-globin genes. Three origins consist of G+C-rich sequences enriched in CpG dinucleotides. The fourth origin is A+T rich. Together with previous work, these data reveal that the insulator origin has unmethylated CpGs, hyperacetylated histones H3 and H4, and lysine 4-methylated histone H3. In contrast, opposite modifications are observed at the other G+C-rich origins. We also show that the whole region, including the stretch of condensed chromatin, replicates early in S phase in these cells. Therefore, different early-firing origins within the same locus may have opposite patterns of epigenetic modifications. The role of insulator elements in DNA replication is discussed.

This article has been cited by other articles:

• Hayashida, T., Oda, M., Ohsawa, K., Yamaguchi, A., Hosozawa, T., Locksley, R. M., Giacca, M., Masai, H., Miyatake, S. (2006). Replication Initiation from a Novel Origin Identified in the Th2 Cytokine Cluster Locus Requires a Distant Conserved Noncoding Sequence. J. Immunol. 176: 5446-5454 [Abstract] [Full Text]  
• Sasaki, T., Ramanathan, S., Okuno, Y., Kumagai, C., Shaikh, S. S., Gilbert, D. M. (2006). The Chinese Hamster Dihydrofolate Reductase Replication Origin Decision Point Follows Activation of Transcription and Suppresses Initiation of Replication within Transcription Units. Mol. Cell. Biol. 26: 1051-1062 [Abstract] [Full Text]  
• Wang, J., Liu, H., Lin, C. M., Aladjem, M. I., Epner, E. M. (2005). Targeted Deletion of the Chicken {beta}-Globin Regulatory Elements Reveals a Cooperative Gene Silencing Activity. J. Biol. Chem. 280: 23340-23348 [Abstract] [Full Text]  
• Kemp, M. G., Ghosh, M., Liu, G., Leffak, M. (2005). The histone deacetylase inhibitor trichostatin A alters the pattern of DNA replication origin activity in human cells. Nucleic Acids Res 33: 325-336 [Abstract] [Full Text]  
• Ghosh, M., Liu, G., Randall, G., Bevington, J., Leffak, M. (2004). Transcription Factor Binding and Induced Transcription Alter Chromosomal c-myc Replicator Activity. Mol. Cell. Biol. 24: 10193-10207 [Abstract] [Full Text]  
• Gomez, M., Brockdorff, N. (2004). Heterochromatin on the inactive X chromosome delays replication timing without affecting origin usage. Proc. Natl. Acad. Sci. USA 101: 6923-6928 [Abstract] [Full Text]  
• Wang, L., Lin, C.-M., Brooks, S., Cimbora, D., Groudine, M., Aladjem, M. I. (2004). The Human {beta}-Globin Replication Initiation Region Consists of Two Modular Independent Replicators. Mol. Cell. Biol. 24: 3373-3386 [Abstract] [Full Text]