How the cell nucleus is functionally and dynamically organized is a central question to understanding basic cellular processes including genome organization and transcriptional regulation. The interphase of both animal and plant nuclei contain morphologically distinct, non-membrane-bounded subnuclear organelles that are collectively called nuclear bodies. Although accumulating evidence suggests that nuclear bodies play important roles in gene regulation and changes in the morphology and constitution of nuclear bodies have been associated with diseases, the precise function and regulatory mechanisms of nuclear body biogenesis in transcriptional regulation remain poorly understood. One major challenge has been the lack of genetic models to delineate the functions of nuclear bodies in the context of transcriptional regulation by cell signaling pathways. The long-term goal of the PI's laboratory is to utilize the photobody ? a photoreceptor-containing, photosensory subnuclear domain ? and light signaling in Arabidopsis as a genetic model to elucidate the function of nuclear bodies in cell signaling and transcriptional regulation. The current data support the central hypothesis that photobodies are gene regulatory hubs where a subset of light responsive genes is regulated by a transactivation mechanism that couples gene activation with the degradation of transcription factors. This hypothesis has been formulated on the basis of the PI's previous molecular genetic studies on two novel light signaling components required for photobody biogenesis, named HEMERA and HERMES, and on the preliminary result showing that a subset of light-responsive genes are spatially positioned to photobodies. Here the PI plans to test this central hypothesis by the following specific aims: (1) Determine the photobody- associated and HEMERA-mediated transcriptional activation mechanism; (2) Determine the role of HERMES in the function and biogenesis of photobodies; (3) Determine the mechanism of genome organization by photobodies. The proposed research is innovative, because it utilizes the photobody and photoreceptor signaling in Arabidopsis as a genetic model to investigate the enigmatic mechanisms of nuclear organization ? the function and biogenesis of nuclear bodies in genome organization and transcriptional regulation. The proposed research is significant, because it is expected to uncover novel mechanisms linking nuclear body biogenesis and specific mechanisms of transcriptional regulation. Because basic mechanisms of gene regulation are conserved in plants, fungi, and animals, a better understanding of the function of photobodies in Arabidopsis will contribute to understanding of the evolutionarily conserved principles of genome organization and transcriptional regulation and thus will ultimately enhance our understanding of their misregulation in human diseases.
The proposed research is relevant to public health because the discovery of evolutionarily conserved mechanisms of genome organization is ultimately expected to increase understanding of how misregulation of nuclear organization leads to alterations in gene expression and genome instability in human diseases such as cancer. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disability.
