Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci.
Replicative senescence is the state of irreversible proliferative arrest that occurs as a concomitant of progressive telomere shortening. By using cDNA microarrays and the gabriel system of computer programs to apply domain-specific and procedural knowledge for data analysis, we investigated global changes in gene transcription occurring during replicative senescence in human fibroblasts and mammary epithelial cells (HMECs). Here we report the identification of transcriptional "fingerprints" unique to senescence, the finding that gene expression perturbations during senescence differ greatly in fibroblasts and HMECs, and the discovery that despite the disparate nature of the chromosomal loci affected by senescence in fibroblasts and HMECs, the up-regulated loci in both types of cells show physical clustering. This clustering, which contrasts with the random distribution of genes down-regulated during senescence or up-regulated during reversible proliferative arrest (i.e., quiescence), supports the view that replicative senescence is associated with alteration of chromatin structure.
Zhang
Hong
H
Departments of Genetics and Medicine, Stanford University School of Medicine, Stanford, CA 94305-5120, USA.
Pan
Kuang-Hung
KH
Cohen
Stanley N
SN
D001940:Breast / Q000166:cytology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation