TY - JOUR
T1 - Differential methylation of hypoxanthine phosphoribosyltransferase genes on active and inactive human X chromosomes
AU - Yen, P. H.
AU - Patel, P.
AU - Chinault, A. C.
AU - Mohandas, T.
AU - Shapiro, L. J.
PY - 1984
Y1 - 1984
N2 - Previous theoretical considerations and some experimental data have suggested a role for DNA methylation in the maintenance of mammalian X chromosome inactivation. The isolation of specific X-encoded sequences makes it possible to investigate this hypothesis directly. We have used cloned fragments of the human hypoxanthine phosphoribosyltransferase (HPRT) gene and methylation-sensitive restriction enzymes to study methylation patterns in genomic DNA of individuals with different numbers of X chromosomes and in somatic cell hybrid lines containing human X chromosomes that are either active or inactive or have been reactivated by treatment with 5-azacytidine. The results of these analyses show that there is hypomethylation of active X chromosomes relative to inactive X chromosomes in the 5' region of this gene. In the middle region of the gene, however, a site that is consistently undermethylated on inactive X chromosomes was identified. Taken together, the data suggest that the overall pattern of methylation, rather than methylation of specific sites, plays a role in the maintenance of X chromosome inactivation.
AB - Previous theoretical considerations and some experimental data have suggested a role for DNA methylation in the maintenance of mammalian X chromosome inactivation. The isolation of specific X-encoded sequences makes it possible to investigate this hypothesis directly. We have used cloned fragments of the human hypoxanthine phosphoribosyltransferase (HPRT) gene and methylation-sensitive restriction enzymes to study methylation patterns in genomic DNA of individuals with different numbers of X chromosomes and in somatic cell hybrid lines containing human X chromosomes that are either active or inactive or have been reactivated by treatment with 5-azacytidine. The results of these analyses show that there is hypomethylation of active X chromosomes relative to inactive X chromosomes in the 5' region of this gene. In the middle region of the gene, however, a site that is consistently undermethylated on inactive X chromosomes was identified. Taken together, the data suggest that the overall pattern of methylation, rather than methylation of specific sites, plays a role in the maintenance of X chromosome inactivation.
UR - http://www.scopus.com/inward/record.url?scp=3042919762&partnerID=8YFLogxK
U2 - 10.1073/pnas.81.6.1759
DO - 10.1073/pnas.81.6.1759
M3 - Article
C2 - 6324214
AN - SCOPUS:3042919762
SN - 0027-8424
VL - 81
SP - 1759
EP - 1763
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6 I
ER -