Extinction of albumin gene expression in a panel of human chromosome 2 microcell hybrids

Journal Article · Thu Feb 01 04:00:00 EST 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0058· OSTI ID:508335

Cerosaletti, K M; Fournier, R E.K. ^[1]

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1. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)

Expression of the serum albumin gene is extinguished in rat hepatoma microcell hybrids that retain mouse chromosome 1. These data define a trans-dominant extinguisher locus, Tse-2, on mouse chromosome 1. To localize the human TSE2 locus, we prepared and characterized rat/human microcell hybrids that contained either human chromosome 1 or chromosome 2, the genetic homologues of mouse chromosome 1. Rat hepatoma microcell hybrids retaining a derivative human chromosome 1 [der 1 t(1;17)(p34.3;q11.2)] expressed their serum albumin genes at levels similar to those of parental hepatoma cells. In contrast, microcell transfer of human chromosome 2 into rat hepatoma recipients produced karyotypically heterogeneous collections of hybrid clones, some of which displayed dramatic albumin extinction phenotypes. For example, albumin mRNA levels in hapatoma x fibroblast whole-cell hybrids. Expression of several other liver genes, including {alpha}1-antitrypsin, aldolase B, alcohol dehydrogenase, and phosphoenolpyruvate carboxykinase, was also affected in some of the microcell hybrids, but expression of these genes was no concordant with expression of albumin. Hybrid segregants were prepared from the albumin-extinguished hybrids, and reexpression of albumin mRNA and protein was observed in sublines that had lost or fragmented human chromosome 2. Finally, expression of mRNAs encoding the liver-enriched transactivators HNF-1, HNF-4, HNF-3{alpha}, and HNF-3{beta} was not affected in any of the chromosome 2-containing hybrids. These data define and map a genetic locus on human chromosome 2 that extinguishes albumin gene expression in trans, and they suggest that TSE2-mediated extinction is independent of HNF-1, -4, -3{alpha}, and -3{beta} expression. 61 refs., 2 figs., 3 tabs.

• OSTI ID: 508335
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 31; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ALBUMINS
BIOLOGICAL EXTINCTION
BIOLOGICAL MARKERS
CHROMOSOMAL ABERRATIONS
DNA HYBRIDIZATION
DNA-CLONING
FLUORESCENCE
GENE REGULATION
GENES
GENETIC MAPPING
HEPATOMAS
HUMAN CHROMOSOME 1
HUMAN CHROMOSOME 17
HUMAN CHROMOSOME 2
HYBRIDIZATION
KARYOTYPE
MESSENGER-RNA
PHENOTYPE
RATS
TISSUE DISTRIBUTION
TRANSCRIPTION
TUMOR CELLS