Chromatin structure is intimately related to optimal cellular function and gene expression, any changes to chromatin can have profound effects, including the emergence of cancer.
A small storage solution is required because a single cell can carry two to three metres of DNA. This is accomplished by the chromatin complex, which is made up of histone-protein-coated DNA. Chromosomes are created by the complex folding of chromatin into a multi-layered organisation made up of loops, domains, and compartments in three dimensions. Any changes in chromatin organisation can have major repercussions, including the development of cancer, as the structure of chromatin is strongly linked to gene expression and optimal cellular function.
About 30% of all human malignancies experience "whole genome doubling (WGD)," a process in which the chromosomes in a cell are doubled. This incident results in genomic instability inside the cell, which may result in chromosomal alterations and other mutations that aid in the growth of cancer.
Elisa Oricchio at EPFL and Giovanni Ciriello at UNIL are leading a research team that has now made a brand-new discovery about how WGD feeds cancer. In a study that was published in Nature, the researchers show how a phenomenon known as "loss of chromatin segregation" might affect the cell's 3D chromatin structure.
The study focused on cells that lack the tumour suppressor p53, making them more vulnerable to WGD. They discovered that WGD reduces the segregation of chromatin's structural components, such as domains, loops, and compartments, causing disruption in the cell's carefully orchestrated chromatin organisation.
The end outcome is a mingling of genetic material that is typically kept apart and a "sub-compartment repositioning" of genomic areas in 3D space. Oncogenes, which are genes that aid in the growth of cancer, are subsequently activated as a result of this.
The study additionally found that the impacts of WGD on chromatin structure are relatively independent of implying that chromatin segregation loss chromosomal alterations, and chromosomal instability are complementary processes that promote cancer development.
