title: Positions of pluripotency genes and hepatocyte-specific genes in the nucleus before and after mouse ES cell differentiation.
abstract: Spatial positioning of genes in the cell nucleus plays an important role in the regulation of genomic functions. Evidence for changes in gene positioning associated with transcriptional activity has been reported. However, our understanding of this phenomenon is still quite limited. We examined how pluripotency genes and hepatocyte-specific genes behave during the differentiation of mouse embryonic stem (ES) cells into hepatocytes, by targeting the loci of the Klf4, Nanog, Oct4, Sox2, Cyp7α1, Pck1, Tat, and Tdo2 genes, and using three-dimensional fluorescence in situ hybridization analyses. We found that each gene has a distinctly inherent localization profile in the ES cell nucleus. During differentiation, the Klf4, Nanog, Oct4, Cyp7α1, Pck1, and Tat loci shifted toward the nuclear center, while the Sox2 and Tdo2 loci shifted toward the periphery. The Klf4, Nanog, Oct4, and Tdo2 seem to prefer the outer regions, rather than the inner regions, when they are active. We also found that the radial positioning of the focused genes in the hepatocyte cell nucleus was highly correlated with the local GC content and the gene density of the surrounding region, but not with gene activity.
authors.affiliation: Major in Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Udagawa
authors.affiliation: Major in Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, Tokyo, Japan ohyama@waseda.jp.
authors.forename: T
authors.initials: T
authors.lastname: Ohyama
mesh_terms: D000818:Animals; D001482:Base Composition; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics*; D002874:Chromosome Mapping; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D000090062:Kruppel-Like Factor 4; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*