Jan 10, 2015

Putative G-quadruplex forming sequence signatures in genes differentially transcribed upon loss of BLM or WRN helicases

BioRxiv : the Preprint Server for Biology
John A Smestad, L James Maher

Abstract

Putative G-quadruplex-forming sequences (PQS) have long been implicated in regulation of DNA replication and transcription, though their actual roles are unknown. To gain insight into potential PQS transcriptional function, we map and analyze PQS motifs in promoters of genes differentially-expressed in Bloom Syndrome (BS) and Werner Syndrome (WS), two human genetic disorders resulting in loss of PQS-interacting RecQ helicases. Non-B-DNA structures at PQS might be stabilized in these syndromes. For BS and WS we demonstrate that PQS promoter abundance is generally higher in down-regulated genes and lower in up-regulated genes, and show that these effects are position-dependent. To interpret these correlations we determined genome-wide PQS correlations with transcription using epigenetic information to predict gene expression. We report that 33% and 35% of analyzed PQS positions in promoter antisense and sense strands, respectively, displayed statistically-significant correlation with gene expression. Of these statistically-significant positions, 100% and 84% on antisense and sense strands, respectively, were correlated with reduced expression. This suggests that promoter PQS repress transcription. Finally, we report neural networ...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Guanosine
Biological Neural Networks
Bloom Syndrome
Genes
Regulation of Biological Process
Werner Syndrome
Transcription, Genetic
RecQ Helicases
Nucleic Acid Sequencing

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