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An epigenetic phenomenon involves heritable changes in the structure and function of the genome over and above the DNA sequence. This layer of information is also referred to as Epigenome. Epigenetic information is encoded in the reversible chemical modifications of histone proteins, DNA. These epigenetic modifications act as the main drivers of the cellular differentiation and de-differentiation, establishing an “epigenetic memory” that robustly maintains cell identity and can represent a formidable barrier to cellular reprogramming. Loss of cell identity can result from aberrations in the epigenetic circuits of protein-protein and protein-DNA interactions that maintain the stable inheritance of the modified chromatin states. This epigenetic layer of genome regulation is increasingly linked to the human disease. A few recent reports have demonstrated the engineering of the transcriptional effectors that allow the targeted manipulation of the epigenetic landscape also known as epigenome engineering and/or epigenome editing. This innovative Epigenome engineering framework has opened a window of opportunity towards controlled switching of the epigenetic states as discovery and application tools (including therapeutics) within a wider synthetic biology framework. 

Targeting epigenomic modifications

One of the main principles of epigenomic editing is the targeting of enzymes to specific regions of DNA. For example, targeting a histone methylase enzyme to a specific DNA sequence could increase histone methylation in that region. There have been several different ways of achieving specific targeting, including transcription activator-like effector proteins (TALEs) or zinc finger proteins. The most commonly used method now is using a modified CRISPR-Cas9 system. Whilst the classic use of CRISPR involves using the Cas9 enzyme to introduce targeted double stranded breaks, epigenomic modifications can be introduced using an inactivated or 'dead' Cas9 (dCas9). Different enzymes can be conjugated to dCas9 and will then be specifically localised to the DNA sequence specified by the CRISPR system. In 2015, researchers conjugated CRISPR-dCas9 to the catalytic core of p300, an acetyltransferase enzymes. This allowed them to induce localised acetylation of histone proteins and subsequent transcriptional activation.

 

 

 

 

 

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About the author

View full profile Hari Raj Singh from Munich

I am a life science researcher with a strong belief that the 21st century is going to be the century of biology touching every aspect of modern human life. I am very excited about the prospects of the new and highly consequential field of synthetic biology. I believe in the power of innovation and that the innovation in life science in particular will positively impact every aspect of human endeavour in the coming decades. I also think that “Synthetic biology driven global bio-economy is our real genuine chance on alleviating global poverty”. This is our moment as life science researchers to provide sustainable growth engines in the form of life science driven disruptive-innovations fueled by our desire to better understand the biological systems and our ability to re-purpose the biological systems; to ultimately bring a paradigm shift in the economic model, what I call the bio-economic model. In future, I am looking forward to the opportunities in this direction with a focus on bottom-up disruptive innovation, which would require very close collaborative efforts from academia, industry and entrepreneurs and a bit of paradigm shift in government policies towards catalyzing the same. I have been and i continue to develop my personal and professional competencies towards creating these aforementioned opportunities, which would help me to contribute and move forward this broader vision that I have and that I very strongly believe in. I think engineering approaches to the understanding of the biological systems that the field of synthetic biology promises to offer is not only going to enhance our understanding in the basic biological research and life science innovation but also it will fuel advances in Physics, Mathematics, Chemistry and Engineering. I am excited about the possibilities and want to be part of it.

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