We have demonstrated that genomic elements such as promoters and enhancers are extensively intertwined with one another genome-wide to form functional transcriptional foci in the nuclei for specific and coordinated transcription regulation. More importantly, we demonstrated genetic variations in regulatory elements involved in chromatin-folding architectures could alter higher-order chromatin interaction architecture and impact gene transcription controls, and thus potentially cause diseases. We are also applying the integrated genomics approach to study internal and external signals and protein factors that orchestrate the 3-D changes of chromatin-interaction architectures and alter the outcomes of gene expression. Furthermore, the induction time courses could provide a system to study the dynamic changes of chromatin structure and transcription regulation in the fourth-dimensional (4-D) space.
Overall, our studies have provided a new dimension of combinatorial controls of gene transcription within the context of chromatin looping architecture in eukaryotic genomes. The work has paved the way toward presenting 3-D topographic maps of human genomes for better understanding of their functions in health and disease.
Our pioneering efforts in technology development have necessitated that we also concomitantly develop new computational tools to process and analyze the unique types of genomic data that our technology has generated. My recent interests in computational analysis are to integrate multi-level genomic data in order to construct multi-dimensional regulatory networks to ultimately elucidate the complex processes that regulate gene transcription using a systems approach.