Mammalian X chromosome inactivation: Testing the hypothesis of transcriptional control

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Abstract
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 wildtype 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.