A National Cheng Kung University (NCKU) research team last week said it had made a key discovery about aging, shedding light on the mysteries of a process whose intricacies researchers have long puzzled over and dedicated many hours of study to.
Research team leader Chiang Jung-hsien (蔣榮先), from the university’s Department of Computer Science and Information Engineering, said the researchers found that aging is associated with a cell’s nuclear pore complexes (NPCs) — pores in the nuclear envelope of human cells that allow molecules to pass in and out of the cell’s nucleus — as an active participant in gene silencing and the formation of peripheral heterochromatin.
The groundbreaking study was carried out by NCKU, Canada’s University of Alberta and the US’ Institute for Systems Biology, and was published in the Feb. 28 issue of the journal Cell.
The paper, titled A Role for the Nucleoporin Nup170p in Chromatin Structure and Gene Silencing, describes the finding made by the seven-member research team that the role which yeast NPC protein Nup170p plays in subtelomeric gene silencing is linked to its association with the chromatin-remodeling complex.
Chiang said that the aging of cells is closely related to the length of the telomore, which is the section at the end of a chromatid that stops the genes in chromosomes from degrading. Each time a cell divides, the telomere gets shorter and eventually leads to cell death, Chiang added.
However, scientists have until now been unclear as to what functional role NPCs play in establishing and maintaining distinct chromatin domains within living cells.
“Our team has discovered that the binding of Nup170p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope, which provides a comprehensive roadmap that leads to the conclusion that Nup170p plays a physiological role at telomeres,” Chiang said.
The team also showed that Nup170p interacts with regions of the genome that contain ribosomal proteins and subtelomeric genes, where it functions as a repressor of transcription.
“This is the first time that functional interactions between Nup170p and chromatin domains that generally reside adjacent to the nuclear envelope, including subtelomeric and telomeric regions, has been shown,” Chiang said.
“Our results establish the NPC as an active participant in silencing and the formation of peripheral heterochromatin,” the study said.
The members of the team are experienced academics in their respective fields, with those from the University of Alberta taking charge of cell biology, those from the Institute for Systems Biology being responsible for profiling gene expression and the NCKU researchers focusing on bioinformatics computing.
The study is a preliminary effort toward gaining a comprehensive understanding of the aging mechanism, Chiang said, adding that the project is ongoing and more research on the subject will be carried out in the near future.