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Molecular and Cellular Biology, May 2006, p. 3707-3717, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3707-3717.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mapping of DNA Replication Origins to Noncoding Genes of the X-Inactivation Center

Rebecca K. Rowntree and Jeannie T. Lee*

Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114

Received 27 February 2006/ Returned for modification 28 February 2006/ Accepted 3 March 2006

In mammals, few DNA replication origins have been identified. Although there appears to be an association between origins and epigenetic regulation, their underlying link to monoallelic gene expression remains unclear. Here, we identify novel origins of DNA replication (ORIs) within the X-inactivation center (Xic). We analyze 86 kb of the Xic using an unbiased approach and find an unexpectedly large number of functional ORIs. Although there has been a tight correlation between ORIs and CpG islands, we find that ORIs are not restricted to CpG islands and there is no dependence on transcriptional activity. Interestingly, these ORIs colocalize to important genetic elements or genes involved in X-chromosome inactivation. One prominent ORI maps to the imprinting center and to a domain within Tsix known to be required for X-chromosome counting and choice. Location and/or activity of ORIs appear to be modulated by removal of specific Xic elements. These data provide a foundation for testing potential relationships between DNA replication and epigenetic regulation in future studies.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Dept. of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114. Phone: (617) 726-5943. Fax: (617) 726-6893. E-mail: lee{at}molbio.mgh.harvard.edu.

Molecular and Cellular Biology, May 2006, p. 3707-3717, Vol. 26, No. 10
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.10.3707-3717.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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