Transcription factor co-occupancy shapes the somatic mutational landscapes across regulatory regions in liver cancer
Both global and local chromatin structure influence the heterogeneous distribution of somatic mutations across the cancer genome. For instance, at the local scale, DNA regions bound by transcription factors (TF) and other chromatin-associated proteins display elevated somatic mutation rates, due to variable DNA damage and repair at these protein-bound sites. However, the contribution of TF…
The distribution of somatic mutations in cancer genomes is influenced by both global and local chromatin structure. At the local level, DNA regions bound by transcription factors (TF) and other chromatin-associated proteins exhibit higher mutation rates. However, the role of TF co-binding in variations of somatic mutation rates has not been extensively studied.
This study combines data from whole-genome sequencing of liver cancer samples with Chromatin Immunoprecipitation sequencing (ChIP-seq) profiles for over 150 TFs and chromatin-associated proteins in the liver cancer cell line HepG2. The results indicate that TF co-occupancy significantly impacts local mutational landscapes, with somatic mutation rates varying considerably across different TFs and co-binding combinations.
Moreover, the magnitude and spatial distribution of mutation rates at TF binding sites differ between promoters and enhancers, likely due to local chromatin accessibility and architecture. Notably, NFIA, a transcription factor, maintains elevated mutation rates at its binding sites regardless of the presence of co-binding proteins.
These findings suggest that combinatorial TF co-occupancy and local chromatin architecture play crucial roles in determining somatic mutation rates across regulatory regions in liver cancer.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
