title: Polymorphic X-chromosome inactivation of the human TIMP1 gene.
abstract: X inactivation silences most but not all of the genes on one of the two X chromosomes in mammalian females. The human X chromosome preserves its activation status when isolated in rodent/human somatic-cell hybrids, and hybrids retaining either the active or inactive X chromosome have been used to assess the inactivation status of many X-linked genes. Surprisingly, the X-linked gene for human tissue inhibitor of metalloproteinases (TIMP1) is expressed in some but not all inactive X-containing somatic-cell hybrids, suggesting that this gene is either prone to reactivation or variable in its inactivation. Since many genes that escape X inactivation are clustered, we examined the expression of four genes (ARAF1, ELK1, ZNF41, and ZNF157) within approximately 100 kb of TIMP1. All four genes were expressed only from the active X chromosome, demonstrating that the factors allowing TIMP1 expression from the inactive X chromosome are specific to the TIMP1 gene. To determine if this variable inactivation of TIMP1 is a function of the hybrid-cell environment or also is observed in human cells, we developed an allele-specific assay to assess TIMP1 expression in human females. Expression of two alleles was detected in some female cells with previously demonstrated extreme skewing of X inactivation, indicating TIMP1 expression from the inactive chromosome. However, in other cells, no expression of TIMP1 was observed from the inactive X chromosome, suggesting that TIMP1 inactivation is polymorphic in human females.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Anderson
authors.forename: C J
authors.initials: CJ
authors.lastname: Brown
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006822:Hybrid Cells; D008214:Lymphocytes; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1