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.
Subject(s)
Fibroblasts/metabolism , Gene Silencing , Hybrid Cells/metabolism , Liver/metabolism , Animals , Cell Line, Tumor , Cellular Reprogramming/genetics , Epigenomics , Gene Expression Profiling , Gene Expression Regulation , Liver/cytology , Oligonucleotide Array Sequence Analysis , Proteins/genetics , Proteins/metabolism , Rats , Reproducibility of Results , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
The title compound, C(7)H(8)N(2)O(4), crystallizes as a zwitterion, with mol-ecules organized into mol-ecular sheets via carbox-yl-carboxyl-ate and N(+)-Hâ¯carboxyl-ate contacts. These sheets are constructed from translationally related mol-ecules that further link to neighboring motifs via π-stacking [centroid-centroid distance 3.504â (3)â Å] and weak C-Hâ¯O contacts.
