11 research outputs found
Extinction of gene expression in somatic cell hybrids. a reflection of important regulatory mechanisms?
Extinction in somatic cell hybrids is a multifactorial process that leads to loss of cell-type-specific gene expression. The underlying mechanisms are thought to mirror, at least in part, the repertoire of regulatory mechanisms controlling mammalian cell differentiation
Extinction of tyrosine aminotransferase gene activity in somatic cell hybrids involves modification and loss of several essential transcription factors
Extinction is defined as the loss of cell type-specific gene expression that occurs in somatic cell hybrids
derived by fusion of cells with dissimilar phenotypes. To explore the basis of this dominant-negative
regulation, we have studied the activities of the control elements of the liver-specific gene encoding tyrosine
aminotransferase (TAT) in hepatoma/fibroblast hybrid crosses. We show that extinction in complete somatic
cell hybrids is accompanied by the loss of activity of all known cell type-specific control elements of the TAT
gene. This inactivity is the result of first, lack of expression of genes coding for the transcriptional activators
HNF4 and HNF3[~ and HNF33,, which bind to essential elements of the enhancers; and second, loss of in vivo
binding and activity of ubiquitous factors to these enhancers, including CREB, which is the target for
repression by the tissue-specific extinguisher locus TSE1. Complete extinction of TAT gene activity is
therefore a multifactorial process affecting all three enhancers controlling liver-specific and hormone-inducible
expression. It results from lack of activation, rather than active repression, and involves both
post-translational modification and loss of essential transcriptional activators
Role of cyclic AMP in the control of cell-specific gene expression
Genes have to be expressed in specific cell types at appropriate times of development dependent on external signals. cAMP signaling occurs in all cells, thus raising the question of how this signal transduction pattern is integrated into mechanisms determining cell-specific gene expression. We have analyzed expression of the tyrosine aminotransferase gene as a model to study the basis of this cell type specificity of hormone induction. We found that cell-type-specific expression is generated by combined action of cAMP signal-dependent and liver cell-specific transcription factors. The interdependence of the cAMP response element and an element determining liver cell specificity enables a gene to respond to an ubiquitous signal in a cell-specific manner
Role of cyclic AMP in the control of cell-specific gene expression
Genes have to be expressed in specific cell types at appropriate times of development dependent on external signals. cAMP signaling occurs in all cells, thus raising the question of how this signal transduction pattern is integrated into mechanisms determining cell-specific gene expression. We have analyzed expression of the tyrosine aminotransferase gene as a model to study the basis of this cell type specificity of hormone induction. We found that cell-type-specific expression is generated by combined action of cAMP signal-dependent and liver cell-specific transcription factors. The interdependence of the cAMP response element and an element determining liver cell specificity enables a gene to respond to an ubiquitous signal in a cell-specific manner