Genome-wide analysis of hepatic gene silencing in mammalian cell hybrids

Abstract

Silencing of tissue-specific gene expression in mammalian somatic cell hybrids is a well-documented epigenetic phenomenon which is both profound (involving a large number of genes) and enigmatic. Our aim was to utilize whole-genome microarray analyses to determine the true extent of gene silencing on a genomic level. By comparing gene expression profiles of hepatoma×fibroblast cell hybrids with those of parental cells, we have identified over 300 liver-enriched genes that are repressed at least 5-fold in the cell hybrids, the majority of which are repressed at least 10-fold. Also, we identify nearly 200 fibroblast-enriched genes that are repressed at least 5-fold. Silenced hepatic genes include several that encode transcription factors and proteins involved in signal transduction pathways. These data suggest that extensive reprogramming occurs in cell hybrids, leading to a nearly global (although not complete) loss of tissue-specific gene expression.

Genome-wide analysis of hepatic gene silencing in hepatoma cell variants

“…Finally, Tfap2b (AP-2 related transcription factor) is a transcription activator involved in early embryogenesis [45]. We previously reported a genome-wide analysis of gene silencing in hepatoma × fibroblast whole cell hybrids [22]. We reported approximately 300 genes that were repressed >5-fold.…”

“…Notably, only a modest number of candidate genes (Oncecut1, Hhex, Igfbp1 as well as Hnf1a and Hnf4a if the threshold is lowered to 3-fold) are shared between these two cell model systems. Candidate genes identified in the previous study fell into three categories: Wnt pathway, growth hormone signaling and the HNF network [22]. Candidate genes identified in the current study included 14 genes that appear to have little in common (see Table 3), except that they appear to be involved in transcriptional and/or developmental regulatory pathways.…”

“…Genome-wide repression of liver-specific gene expression in hepatoma× fibroblast somatic cell hybrids was recently reported [22]. We compared repression profiles of the cell hybrids with that of the hepatoma variant cell lines in the current study with regard to candidate genes identified.…”

“…Promoter analysis (GeneCard) was used to identify which genes contain HNF1α binding sites in proximal promoter regions.Fig.5. Comparison of candidate genes identified from whole genome analysis of hepatoma × fibroblast whole cell hybrids[22] and the current study of hepatoma variants. Genes shown were repressed > 5 fold compared to hepatoma parental cells and are members of transcriptional activation pathways.…”

The shock of being united and symphiliosis

“…44 cells of various kind is thought to affect cancer progression by combining their properties, and by triggering symphilial instabilities, not unlike it is envisioned by the "diverge, merge, and diverge" model of plant evolution. 34,69,70 Finally, the fusion of different cell types often results in the loss of gene expression patterns specific to either of the parental types, a phenomenon known as extinction 44,71 and is manifested as dedifferentiation, a feature of aggressive cancers. Extinction also has the potential to revert the cell to an atavistic state.…”