Asynchronous replication of homologous loci on human active and inactive X chromosomes.
The two X chromosomes in mammalian females replicate asynchronously, the inactive later than the active one. Using BrdUrd-sensitive restriction and UV irradiation to identify newly synthesized DNA directly on Southern blots, and restriction fragment length differences to discriminate alleles on active and inactive human X chromosomes, we examined the replication of hypoxanthine phosphoribosyltransferase (HPRT) and clotting factor IX (F9) loci in clonal populations of mouse-human hybrids. We find that HPRT replicates at different times during the period of DNA synthesis (S phase), depending on its activity: It replicates in early S phase, when expressed (on the active X chromosome), and in late S phase when silent (on the inactive X chromosome). Furthermore, when reactivated, the derepressed locus is earlier replicating, supporting a relationship between replication and transcription. Neither F9 allele is expressed in these cells, and both replicate in the second half of S phase, (slightly earlier on active than on inactive X chromosome).
Schmidt
M
M
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Migeon
B R
BR
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D001973:Bromodeoxyuridine; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D004261:DNA Replication; D005260:Female; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007399:Interphase; D051379:Mice; D008938:Mitosis; D015183:Restriction Mapping; D014960:X Chromosome
D015342:DNA Probes; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D001973:Bromodeoxyuridine