Research interests: My research program investigates the regulation of gene expression. The anthocyanin biosynthetic pathway in maize is the focus of our work, as it provides an exceptionally tractable system for genetic, biochemical and molecular approaches. A major emphasis in our research is to investigate how the regulatory genes of this pathway are controlled. These regulatory genes, which encode transcription factors that activate the anthocyanin biosynthetic genes, have multiple alleles that produce distinct developmental and tissue-specific patterns of anthocyanin pigments. In addition, we have identified negatively acting modifier genes that reduce the expression of the biosynthetic and regulatory genes. Identifying the cis-acting sequences regulating differential expression, and factors that interact with these sequences should provide important information on mechanisms of gene regulation, applicable to numerous plant systems. In addition, the availability of regulatory sequences that can control expression in distinct tissues and developmental stages will greatly enhance the potential of genetic engineering. We are also using this system to investigate mechanisms of gene silencing, which has a fundamental role in development and has recently become a major problem with genetic engineering approaches to crop improvement.
We use both forward and reverse genetic approaches to study paramutation,
the regulation of transposable elements and transgene silencing. Paramutation is a mitotically and meiotically heritable change in gene
expression that is induced by allele interactions. We have demonstrated that the heritable change is accompanied by a ten- to
twenty-fold reduction in transcription. Recently we have used a combination of classical genetics, genomics, and molecular methods to
identify and characterize the minimal sequences required for paramutation, which map within 95-102 kbp upstream of the transcription
initiation site. We have also identified multiple mutations in other genes required for the establishment and maintenance of
paramutation. We have shown that these mutants also activate previously silent transposable elements and transgenes, indicating that the
wild type proteins are required for multiple gene-silencing processes. Experiments are in progress to clone the genes represented by
these mutations and determine their role in gene silencing. As heritable changes in chromatin structure are clearly involved in the
establishment and maintenance of distinct transcription states we are also pursuing a functional genomics approach to understand
chromatin-level control of gene expression in both maize and Arabidopsis.
Chandler VL. Feb 2007. Paramutation: From Maize to Mice. Cell, 128:641-645.
Alleman M, Sidorenko L, McGinnis K, Seshadri V, Dorweiler JE, White J, Sikkink K, Chandler VL. Jul 2006. An RNA-dependent RNA polymerase is required for paramutation in maize. Nature, 442:295-8
McGinnis KM, Springer C, Lin Y, Carey CC, Chandler V. Jul 2006. Transcriptionally silenced transgenes in maize are activated by three mutations defective in paramutation. Genetics, 173:1637-47.
McGinnis K, Chandler V, Cone K, Kaeppler H, Kaeppler S, Kerschen A, Pikaard C, Richards E, Sidorenko L, Smith T, Springer N, Wulan T. Jan 2005. Transgene-induced RNA interference as a tool for plant functional genomics. Methods Enzymol, 392:1-24.