Unleashing the power of epigenetic editing: A new modular system allows precise control of chromatin modifications

Thursday - May 9 2024, 22:00 UTC - 1 year ago

A study published by the Hackett Group at EMBL Rome introduces a new modular epigenome editing platform that allows precise control of chromatin modifications at any location in the genome. This technology has already revealed new insights into the role of chromatin marks in gene regulation and has the potential to greatly advance our understanding of cellular processes.

Understanding the complex mechanisms of gene regulation at the molecular level is a fundamental goal in modern biology. This intricate process involves a delicate interplay between proteins called transcription factors, DNA regulatory regions, and epigenetic modifications. These chemical alterations change the structure of chromatin, the material that makes up chromosomes, and collectively make up the epigenome .

To shed light on the impact of these modifications on gene expression, researchers from the Hackett Group at EMBL Rome have developed a powerful epigenetic editing technology that allows precise control of chromatin modifications at any location in the genome.Published in Nature Genetics on May 9, the study presents a modular epigenome editing platform that enables scientists to program nine biologically important chromatin marks at specific DNA locations .

This system not only provides a means to study the impact of each chromatin modification on gene expression, but it also sheds light on the causal relationships between chromatin marks and their biological effects.One of the key challenges in deciphering the role of chromatin modifications in gene regulation is dissecting their individual contributions in such a complex process. By integrating data from previous studies on chromatin distribution in healthy and diseased cells, gene expression analysis, and the effects of perturbing specific genes, researchers have been able to attribute functions to different chromatin marks .

However, understanding the causal relationship between these marks and gene regulation has proven difficult.This new epigenome editing platform, based on a widely used technology called CRISPR, has provided a solution to this problem. The precise perturbations made possible by this technology allowed researchers to carefully study the impact of each chromatin modification on gene expression. In addition, the team utilized a reporter system to measure changes in gene expression at the single-cell level and investigate how changes in the DNA sequence can influence the effects of each chromatin mark .

The results of this study have revealed new insights into the role of chromatin marks in gene regulation. For instance, the researchers discovered a new function for H3K4me3, a chromatin mark previously thought to be a result of transcription. Contrary to expectations, the team found that adding H3K4me3 to specific DNA locations can increase gene transcription on its own.According to Cristina Policarpi, postdoc in the Hackett Group and leading researcher on the impact of chromatin marks on gene regulation, this unexpected result was the most exciting aspect of the study .

The ability to precisely perturb chromatin marks at any location in the genome using this system provides a powerful tool for future functional epigenomic studies.Diego Caprara, a former PhD student at EMBL Rome and first author of the study, also highlights the potential of this new epigenome editing platform. Not only does it offer a means to study the impact of specific chromatin marks on gene regulation, but it also provides a better understanding of the interplay between chromatin modifications, transcription factors, and regulatory DNA sequences .

In summary, this new epigenetic editing technology has the potential to revolutionize our understanding of gene regulation and reveal new insights into the complex mechanisms that govern cellular processes.