Recommendable! Appears to be a major work on this subject by the Garvan Institute of Medical Research in Australia
"Most cancer cells have genomes that are much less methylated than those of normal cells, but whether this loss of methylation, an epigenetic process, has any functional meaning for the cells has long been an unanswered question. Now researchers show that the loss of DNA methylation across the genome changes the timing of DNA replication and alters the shape of the 3-D compartmentalization of DNA, which helps steer gene expression. ...
For the past 25 years or so, Susan Clark and her group at Garvan Institute of Medical Research in Australia have been interested in how epigenetics is involved in cancer. As most cancer cells lose DNA methylation throughout the genome, it was surprising how little was known about the global consequences of the hypomethylation ...
One next step would be “a comparison between healthy cells, precancerous cells, and cancer cells,” ... “What we’ve got represented here is a picture of cancer and aberrant DNA methylation, but that doesn’t just happen all at once. I’d like to see what happens in DNA methylation, 3-D genome organization, and DNA replication timing during the process of oncogenesis.”"
For the past 25 years or so, Susan Clark and her group at Garvan Institute of Medical Research in Australia have been interested in how epigenetics is involved in cancer. As most cancer cells lose DNA methylation throughout the genome, it was surprising how little was known about the global consequences of the hypomethylation ...
One next step would be “a comparison between healthy cells, precancerous cells, and cancer cells,” ... “What we’ve got represented here is a picture of cancer and aberrant DNA methylation, but that doesn’t just happen all at once. I’d like to see what happens in DNA methylation, 3-D genome organization, and DNA replication timing during the process of oncogenesis.”"
From the abstract:
"DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. ..."
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