Deciphering three-dimensional genome structure
Recent technological advancements have allowed us to begin to model complex 3D genome structures in the nucleus. We have modeled the 3D genome structure of the model organism fission yeast using a genomic approach that combines the molecular biology procedure called chromosome conformation capture (3C) and next-generation DNA sequencing. To accurately model this genome structure, we successfully fused microscopy and genomic data.
[In the figure: Modeled 3D structure of the fission yeast genome.]
We showed that distinct chromosomal territories exist in fission yeast and demonstrated that highly transcribed genes, co-regulated genes, and functionally related genes tend to co-localize in the in vivo genome structure. We also identified conserved DNA motifs present at gene promoter regions, likely recognized by transcription factors, which play a role in facilitating those gene associations. We found that our simple model organism, fission yeast, has a functional genome organization similar to the mammalian transcription factories.
This project is supported by The NIH Director’s New Innovator Award and The G. Harold & Leila Y. Mathers Foundation.
Centromeric association of dispersed Pol III genes in fission yeast
We have previously shown that the RNA polymerase III (Pol III) transcription factor complex, TFIIIC, participates in organizing the higher-order genome structure in fission yeast. We have recently found that Pol III transcribed genes can localize to centromeres and contribute to a global genome organization in interphase. We also showed that the centromeric association of Pol III genes is mediated by the condensin complex, which is known to function in chromosome condensation during mitosis, and demonstrated that the centromeric association of Pol III genes participates in chromosome condensation during mitosis. An understanding of the structure of mitotic chromosomes has long been elusive, but our study has now partially resolved this long-standing question.
This project is supported by The V foundation and The Edward Mallinckrodt, Jr. Foundation.
[In the figure: A number of Pol III genes such as tRNA and 5S rRNA genes dispersed throughout the fission yeast genome associate with centromeres. This centromeric association of Pol III genes is mediated by Pol III transcription machinery and condensin complex (top). The centromeric association of Pol III genes likely influences global higher-order chromosome structure, helping mediate formation of numerous chromatin loops derived from centromeres (middle). In mitosis, the centromeric association of Pol III genes contributes to chromosome condensation essential for faithful chromosome segregation (bottom).]