title: Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential.
abstract: The human Werner and Bloom syndromes (WS and BS) are caused by deficiencies in the WRN and BLM RecQ helicases, respectively. WRN, BLM and their Saccharomyces cerevisiae homologue Sgs1, are particularly active in vitro in unwinding G-quadruplex DNA (G4-DNA), a family of non-canonical nucleic acid structures formed by certain G-rich sequences. Recently, mRNA levels from loci containing potential G-quadruplex-forming sequences (PQS) were found to be preferentially altered in sgs1Delta mutants, suggesting that G4-DNA targeting by Sgs1 directly affects gene expression. Here, we extend these findings to human cells. Using microarrays to measure mRNAs obtained from human fibroblasts deficient for various RecQ family helicases, we observe significant associations between loci that are upregulated in WS or BS cells and loci that have PQS. No such PQS associations were observed for control expression datasets, however. Furthermore, upregulated genes in WS and BS showed no or dramatically reduced associations with sequences similar to PQS but that have considerably reduced potential to form intramolecular G4-DNA. These findings indicate that, like Sgs1, WRN and BLM can regulate transcription globally by targeting G4-DNA.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Jay E
authors: JE
authors: Johnson
authors: Kajia
authors: K
authors: Cao
authors: Paul
authors: P
authors: Ryvkin
authors: Li-San
authors: LS
authors: Wang
authors: F Brad
authors: FB
authors: Johnson
mesh_terms: D001483:Base Sequence; D001816:Bloom Syndrome / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D054856:G-Quadruplexes; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D053484:RecQ Helicases / Q000172:deficiency*; D015854:Up-Regulation; D014898:Werner Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D004247:DNA; D053484:RecQ Helicases