TY - JOUR
T1 - Frequent derepression of G6PD and HPRT on the Marsupial inactive X chromosome associated with cell proliferation in vitro
AU - Migeon, Barbara R.
AU - De Beur, Suzanne Jan
AU - Axelman, Joyce
N1 - Funding Information:
These studiesw ere supportedb y NIH Grant HD05465.W e are gratefult o Mohamed M. Khalifa, Alan H. Beggs, Daniel D. Driscoll, and David C. Kaslow for helpful discussions,a nd to Paulette G. Sandersf or her contributionst o theses tudies.W e are gratefult o Drs. P. Samollowa nd J. VandeBerg for providingt he opossumt issues.
PY - 1989/6
Y1 - 1989/6
N2 - X chromosome dosage compensation in Marsupials is like that in eutherian mammals except that the paternal X chromosome is always inactive, and silence of this chromosome is not well maintained. We previously showed that the unstable inactivation of the paternal G6PD allele is associated with the lack of DNA methylation in the 5′ CpG cluster. Even though this CpG island is unmethylated, the paternal allele (marked by an enzyme variant) is at least partially and often severely repressed in most tissues of the opossum, so that factors other than methylation must inactivate the locus. Here we report that when cell cultures are established from these tissues, the silent G6PD locus is derepressed. Although often complete, the extent of derepression differs among tissues and within different cell types in the same tissue, and is not accompanied by obvious changes in the pattern of chromosome replication. Studies of the HPRT locus in these cells show that the paternal HPRT allele also derepresses in cultured cells. These observations suggest that without DNA methylation to maintain the silence of the locus, tissue or cell-specific factors act to repress the silent locus, but are unable to maintain inactivity through cell division, or are lost as cells proliferate in culture.
AB - X chromosome dosage compensation in Marsupials is like that in eutherian mammals except that the paternal X chromosome is always inactive, and silence of this chromosome is not well maintained. We previously showed that the unstable inactivation of the paternal G6PD allele is associated with the lack of DNA methylation in the 5′ CpG cluster. Even though this CpG island is unmethylated, the paternal allele (marked by an enzyme variant) is at least partially and often severely repressed in most tissues of the opossum, so that factors other than methylation must inactivate the locus. Here we report that when cell cultures are established from these tissues, the silent G6PD locus is derepressed. Although often complete, the extent of derepression differs among tissues and within different cell types in the same tissue, and is not accompanied by obvious changes in the pattern of chromosome replication. Studies of the HPRT locus in these cells show that the paternal HPRT allele also derepresses in cultured cells. These observations suggest that without DNA methylation to maintain the silence of the locus, tissue or cell-specific factors act to repress the silent locus, but are unable to maintain inactivity through cell division, or are lost as cells proliferate in culture.
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U2 - 10.1016/0014-4827(89)90262-0
DO - 10.1016/0014-4827(89)90262-0
M3 - Article
C2 - 2721594
AN - SCOPUS:0024343450
SN - 0014-4827
VL - 182
SP - 597
EP - 609
JO - Experimental cell research
JF - Experimental cell research
IS - 2
ER -