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MATAC-Seq: lifting the fog around cell to cell variability


Researchers at the Hamperl lab from the Institute of Epigenetics and Stem Cells (IES), working alongside the Scialdone lab at the institute and Lopes lab in University of Zurich, introduce the innovative approach for accurately mapping the dynamics of accessibility at specific genomic loci.

The researchers from the Hamperl lab in collaboration with the Scialdone lab from the IES have developed an innovative method to precisely navigate the accessibility dynamics at individual genomic loci. This method named Methylation Accessibility of TArgeted Chromatin domain Sequencing (or MATAC-Seq) was validated by electron microscopy in collaboration with the Lopes lab at the University of Zurich and helps lifting the fog around cell to cell variability in DNA accessibility.

As the corresponding author Dr. Hamperl notes “DNA replication origin firing has been considered as a stochastic process despite the fact that the DNA replication timing program in eukaryotic cells is highly reproducible and conserved.” MATAC-Seq allows to unveil distinct changes in individual genomic regions at the single-molecule level, providing insights into their full diversity and dynamics of chromatin states usually masked by other bulk methods.


Implementing this novel tool to predict early and late replication origins in yeast, the team has identified emerging consistent pattern: efficient origin activation is correlated with accessible nucleosome-free region when combined with well-positioned nucleosomes just upstream of the origin.

More generally, such a tool would be beneficial to the wider scientific community: “Based on our findings and the novel method that we developed, researchers can now start to study the heterogeneity of chromatin states surrounding specific origins and any other regulatory region of the genome. Stephan Hamperl highlights. “In the future, this will hopefully lead the way towards therapeutic interventions when DNA replication timing is deregulated in human diseases such as cancer.”

MATAC-Seq, acting as a precise genomic navigator, not only deciphers the heterogeneity of replication origins but also lays the foundation for understanding the regulatory nuances in various biological processes like transcription, replication, and DNA repair.


Read the full publication here.