Overview: I am nominating myself for a NIH Director s Pioneer Award, which ifawarded, I would use to investigate homology-dependent epigenetic mechanisms of generegulation in animal models and eventually humans. One aspect of my research has been tostudy a phenomenon called paramutation, which was discovered in plants and involves allelecommunication that leads to a mitotically and meiotically heritable change in gene expression.My hypothesis is that the paradigm-shifting mechanisms of allele communication, which wehave uncovered operating in plant chromatin, also exists in mammals and could explain theaberrant segregation of certain genetic diseases.I have organized this essay in 3 sections. In Background and Significance, I defineepigenetics, briefly summarize the fields current understanding of mechanisms and discuss itsimportance for understanding a number of human diseases. In Prior and Current Work, Isummarize our prior work on paramutation, using this as a basis for illustrating my approach toscience providing evidence for why this nomination should be considered in the NDPA process.In New Research Direction, I briefly describe the new approaches I am proposing, explain howthis builds on my past work, and discuss why the NDPA process provides a unique opportunityto pursue this work.
| Peterson, Maureen; Chandler, Vicki L; Bosco, Giovanni (2013) High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1. Genes (Basel) 4:226-43 |
| Arteaga-Vazquez, Mario Alberto; Chandler, Vicki Lynn (2010) Paramutation in maize: RNA mediated trans-generational gene silencing. Curr Opin Genet Dev 20:156-63 |
| Lu, Y C; Touzjian, N; Stenzel, M et al. (1990) Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1. J Virol 64:5226-9 |
