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Replication timing properties, of the humanHPRT locus on active, inactive and reactivated X chromosomes

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Somatic Cell and Molecular Genetics

Abstract

X chromosome inactivation is associated with a highly asynchronous pattern of DNA replication at most X-linked loci in females. We studied the human HPRT locus, which is subject to X inactivation and expressed from only the active homolog, with the goal of comparing replication properties between the active and inactive homologs in this region using a fluorescence in situ hybridization approach. We found that in normal female lymphoblasts this locus is replicated in a highly asynchronous manner across a broad, discrete 500–600 kb zone with earliest replication appearing at the gene coding sequence. This general timing profile is maintained in normal male lymphoblasts, as well as in hamster x human hybrid cells containing the active human X chromosome. However, the inactive human X chromosome in the hamster cell background does not appear to function in a fully equivalent manner to the normal inactive X chromosome in female cells. Furthermore, reactivation of the inactive human X chromosome in a hamster x human hybrid system by 5-azacytidine treatment and HAT selection restores early replication at the HPRT gene itself, but does not change the overall domain behavior.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 77030, Houston, Texas

    Prem S. Subramanian & A. Craig Chinault

  2. Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, 7703, Houston, Texas

    A. Craig Chinault

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  1. Prem S. Subramanian
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  2. A. Craig Chinault
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Subramanian, P.S., Craig Chinault, A. Replication timing properties, of the humanHPRT locus on active, inactive and reactivated X chromosomes. Somat Cell Mol Genet 23, 97–109 (1997). https://doi.org/10.1007/BF02679969

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  • DOI: https://doi.org/10.1007/BF02679969

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