Department of Molecular and Cellular Biochemistry

Lab

Myers Hall 359
(812) 856-0355

Awards

Outstanding Junior Faculty Award
NSF CAREER Award

Research

My laboratory is generally interested in gene regulation, epigenetics, and chromatin structure/function. Our current research combines all of these elements. Changes in gene expression play a central role in development, as well as responses to environmental stimuli/stress. Depending on the situation, hundreds to thousands of genes will show significant changes in expression. A major challenge during these large-scale changes in gene expression is to ensure that changes are restricted to target genes and do not affect the expression of neighboring genes. In animals, CCCTC-binding factor (CTCF) plays a critical role in the formation of chromatin loops and the activity of insulator sequences that separate transcriptional domains. Despite the fact that CTCF homologs are not found in plants, chromatin loops are a significant feature of the Arabidopsis genome, where intragenic "gene loops" often occur between the 5' and 3' regions of genes. The function of these gene loops, as well has how they are formed in the absence of CTCF-type insulator proteins, are currently unclear. Our laboratory has discovered a previously undescribed class of Arabidopsis transcription factors, BORDER (BDR) proteins, that are providing insight into the relationship between the 3-dimensional arrangement of chromatin and transcription. BDR proteins interact with RNA polymerase II (Pol II) and are overrepresented in the 5' and 3' regions of genes containing gene loops. In bdr mutants, the expression of the loop-containing gene is unaffected, however, the expression of genes that are located downstream on the same DNA strand from the loop-containing gene are downregulated. This suggests a model in which BDR interacts with gene loops to prevent the transcription of upstream genes from interfering with the expression of downstream neighbors. In our future research, will use a range of complementary approaches to investigate the role of BDR proteins in gene loops and transcriptional regulation. These will include using HiC and related techniques to determine the requirement for BDR proteins in the formation and/or function of gene loops, using biochemistry to determine the effect of BDR on Pol II elongation and/or pausing, and using the regulation of flowering time as a system to study the role of BDR proteins in development. Because proteins with BDR-like domain structures occur in plants, animals, and yeast, we believe the knowledge gained in these studies will have broad applications, including human health and food security.