New insights into DNA methylation mechanics using high throughput computing algorithms for epigenomics data analysis

Identifier:  TFG:2967

Handle: https://hdl.handle.net/20.500.11797/TFG2967

Authors:  Eizaguirre Suarez, German Telmo

Abstract:
Epigenomic regulation is a complex process mediated by multiple factors. Understanding the functionality of DNA sequences involved in such process is crucial for clinical and research aims. DNA methylation is a crucial epigenetics mark responsible for gene silencing. Hence, motifs extracted from DNA methylation sites include specific DNA words relatable to many crucial biological processes, including cell reprogramming and differentiation. As methylation regulation is suggested to be a cooperative mechanism between different molecules and protein domains, methylation motifs do not necessarily need to appear centred on the methylation target. Instead, steric hindrance between different DNA binding domains should be considered when analysing DNA methylation motifs. If methylation regulator proteins are affected by steric hindrance, then DNA methylation motifs should be positioned at some bases of displacement from the methylation target. We implemented an extensive, genome-wide methylation motif discovery pipeline runnable in Slurm-based HPC clusters. We optimized the pipeline for the analysis of hundreds of displacements in one run. Our pipeline discloses motifs independently of their positioning relative to the DNA methylation target. We study the prevalence of displaced methylation motifs in cell lines at multiple differentiation levels and disclose valuable trends of motif quality at specific displacements from the methylation target. We relate our result to molecular mechanisms involved in differentiation and propose new models for the repression of genes involved in pluripotency.