Mammalian X chromosome inactivation: testing the hypothesis of transcriptional control

Mammalian X chromosome inactivation is generally considered to be a good example of stable transcriptional repression; however, there has been no satisfactory evidence for transcriptional control. We have made a test of the hypothesis of transcriptional control by Northern blot analysis of RNA from a woman heterozygous for a mutant Hpt allele which shows no detectable transcription of wild-type mRNA. Cells from this Hpt+ Hpt- woman were separated into HPRT+ and HPRT- subpopulations by selection in HAT or thioguanine. The HPRT+ population (in which the Hpt+ is on the active X) transcribed normal Hpt mRNA, while the HPRT- population (in which the Hpt+ allele is on the inactive X) did not. These results provide strong support for the hypothesis of transcriptional control.