Mammalian X chromosome inactivation: Testing the hypothesis of transcriptional control

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.