Poster abstracts
Poster number 24 submitted by Adam Richardson
Coordination of G4R1, RNAPII, and AGO proteins to regulate the transcription of developmental genes and proto-oncogenes
Adam E. Richardson (Ball State University, Department of Biology), Josh D. Tompkins (City of Hope, Department of Diabetes Complications & Metabolism), Arthur D. Riggs (City of Hope, Department of Diabetes Complications & Metabolism), Steven N. Akman (St. Francis Roper Cancer Center), James P. Vaughn (Nanomedica Inc.), Philip J. Smaldino (Ball State University, Department of Biology)
Abstract:
Regulation of developmental gene and proto-oncogene transcription is a complex process involving the participation of many proteins. These proteins tightly regulate developmental gene and proto-oncogene expression to prevent uncontrolled, cancerous cell growth and division. One of the many layers in which the expression of these genes is regulated is through G-quadruplex (G4) structures. G4 structures form within guanine-rich regions of DNA and RNA. The guanines self-associate into vertically-stacked planar tetrads, stabilized via Hoogsteen hydrogen-bonding and coordinate bonding with a monovalent cation. The human genome contains 716,310 putative G4 motifs, which are present in upwards of 40% of gene promoters. The degree of enrichment of promoter G4 structures has been shown to correlate with the function of the gene. For example, proto-oncogenes and developmental genes are especially enriched with G4 structures in contrast to tumor suppressor and housekeeping genes. Promoter G4 structures negatively regulate transcription via impeding the transcriptional machinery. The cell can overcome this barrier by using G4 helicases such as G4 Resolvase1 (G4R1) (aliases DHX36 and RHAU), which unwinds G4 structures. AGO2 and RNAPII are also key proteins involved in transcriptional regulation and are binding partners with G4R1. For these reasons, we performed a chromatin immunoprecipitation on chip (ChIP-chip) using antibodies specific to G4R1, RNAPII, and AGO proteins (AGO). We found that G4R1, RNAPII, and AGO binding sites overlap with genes involved with developmental processes, pattern specification processes, and cell fate commitment. Furthermore, under serum starvation, the three proteins co-localized to the enhancer of C-MYC. These data suggest that G4R1, RNAPII, and AGO function together to regulate the transcription of developmental genes and proto-oncogenes.
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Keywords: G4R1, Transcription regulation, Development