A-11: cell type-specific and single-active-X transcription controls of newly found gene in cultured human cells.
We describe the isolation and characterization of a human X-chromosomal gene that is subject to both single-active-X control and tissue-specific control. The A-11 gene was identified by a cDNA that hydridizes to a 3.2-kb EcoR1 fragment of genomic DNA on the long arm of the human X chromosome. A-11 transcripts are normally present in fibroblasts but not in B- or T-lymphoblasts. However, A-11 transcription was activated in four of 11 independent, gamma ray-induced B-lymphoblastoid HLA antigen-loss mutants. Cell hybrids with a human fibroblast-derived active X contained A-11 transcripts but hybrids carrying the human inactive X did not. Azacytidine, a potent inhibitor of DNA methylation, readily reactivated the A-11 locus on the inactive X in hybrid cells, indicating that differential methylation is likely to be involved in the single-active-X control of A-11 transcription in fibroblasts. Failure of cells to remethylate DNA synthesized to repair gamma ray-induced damage may also have resulted in the activation of A-11 transcription among the lymphoblastoid mutants. The A-11 locus provides an opportunity to study the relationship between two types of transcriptional regulation of a gene.
Nadon
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Laboratory of Genetics, University of Wisconsin, Madison 53706.
Korn
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DeMars
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R
D001374:Azacitidine / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005347:Fibroblasts / Q000502:physiology; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008745:Methylation; D009154:Mutation / Q000528:radiation effects; D012326:RNA Splicing; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014960:X Chromosome
D004247:DNA; D001374:Azacitidine