Title

Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci

UMMS Affiliation

Department of Cell Biology

Date

3-11-2003

Document Type

Article

Medical Subject Headings

Breast; Cell Aging; Cell Division; Cell Line; Chromosomes, Human; Epithelial Cells; Female; Fibroblasts; Gene Expression Profiling; Humans; Oligonucleotide Array Sequence Analysis; Up-Regulation

Disciplines

Cell Biology

Abstract

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3251-6. Epub 2003 Mar 7. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

12626749