January 10 2006
9:30 LSB 2320

Dr. Ben Holt, III
Department of Biology, The University of North Carolina at Chapel Hill

From Cradle to Grave: Diverse Functions of the CAAT Box Binding Transcription Factors


Assigning function(s) to each gene in a genome is one of the great challenges for modern biologists. Adding to this challenge, many genes express minor quantitative traits or are essential during some stage of development. Comparative functional genomics is a powerful tool for overcoming these technical difficulties. With this approach to assigning gene function, model organisms such as Arabidopsis thaliana and Caenorhabditis elegans become key reference species for investigating genetic pathways of fundamental importance to fields as diverse as plant development and human health. I am interested in using these model organisms to explore the CCAAT box binding factor (CBF) " an indispensable human transcriptional regulator. From previous biochemical analyses, primarily using mammalian cell lines, CBF was implicated in numerous biomedically important processes, including stem cell and cancer cell proliferation, embryogenesis, and chromatin remodeling. In fact, CBF is found in all human cell types and as much as 25% of the expressed human genes are predicted to be under CBF transcriptional control. Unfortunately, the CBF is essential in mammals, greatly limiting genetic approaches to understanding its function. This is especially restrictive for geneticists wishing to move from cell culture to whole organism studies " a crucial transition for accurate assignments of gene function.

In Arabidopsis, loss-of-function mutations in most CBF genes do not result in lethality. Additionally, due to repeated duplication events, this gene family has expanded greatly in the plant lineage. Mammals have only one gene for each of the 3 CBF subunits, each of which is essential for development. In contrast, Arabidopsis and C. elegans have 36 and 6 CBF subunit genes, respectively. My initial investigations demonstrate that, like mammals, these CBF genes are expressed throughout the developing Arabidopsis plant. Furthermore, there is sufficient functional overlap within the Arabidopsis CBF genes to support viability when there is a lesion in any single member of the group. This presents a unique opportunity to genetically dissect CBF function in a whole organism. During my presentation, I will discuss my research suggesting that several Arabidopsis CBF genes are involved in cell death and disease resistance. Further, I will discuss my future plans to uncover additional CBF-related functions and associate these functions with CBF-regulated gene sets.