Gene Expression 101 with Dr. David Segal

Quick Overview

Dr. David Segal, a professor at UC Davis Genome Center, gave a presentation on gene expression and gene editing at the 2016 FAST Science Summit. He discussed the process of gene expression, where DNA is transcribed into RNA and then translated into protein. He explained how transcription factors can control which genes are turned on and off, and how artificial transcription factors can be designed to target specific genes. He also discussed the use of antisense oligonucleotides to disrupt RNA and prevent protein production. Dr. Segal presented research on using artificial transcription factors and antisense oligonucleotides to reactivate the UBE3A gene in Angelman syndrome mice, showing promising results in turning on the gene and rescuing phenotypes. He emphasized the need to continue exploring and comparing different approaches to find the most effective treatment for Angelman syndrome.

Introduction

In this talk, we will explore the topic of gene expression and its relevance to epigenetics and gene editing. Dr. David Segal, a professor at the UC Davis Genome Center, will provide insights into the use of artificial transcription factors (ATFs) and antisense oligonucleotide therapy (ASOs) for therapeutic purposes, particularly in the treatment of children.

Understanding Gene Expression

Gene expression is a fundamental process in molecular biology, often referred to as the central dogma. It involves the conversion of DNA into RNA, which then leads to the production of proteins. DNA, the genetic material, is composed of four subunits: A, G, C, and T. These subunits interact with each other in a predictable manner, with A always pairing with T and G always pairing with C. The DNA is organized into chromosomes, and each cell in our body contains approximately two meters of DNA.

Transcription Factors and Gene Regulation

To determine which genes are turned on or off, cells utilize transcription factors. These proteins bind to specific regions of DNA, known as binding sites, and help recruit enzymes responsible for transcribing DNA into RNA. Transcription factors can be either activators or repressors, depending on their role in gene regulation. By understanding how natural transcription factors work, scientists can design artificial transcription factors to control gene expression.

Artificial Transcription Factors (ATFs)

One type of artificial transcription factor is the zinc finger protein. These proteins have two main components: a DNA-binding domain and an activation or repression domain. By programming zinc finger proteins to recognize specific DNA sequences, researchers can design artificial transcription factors that target specific genes. Dr. Segal’s lab has successfully used these artificial transcription factors to reactivate the UBE3A gene in mice with Angelman syndrome, leading to the production of the UBE3A protein.

Antisense Oligonucleotide Therapy (ASOs)

Another approach to gene regulation is through antisense oligonucleotide therapy. Antisense oligonucleotides are single-stranded DNA molecules that can bind to RNA molecules. By targeting specific RNA sequences, antisense oligonucleotides can disrupt the production of proteins. In the case of Angelman syndrome, researchers have developed antisense oligonucleotides that target the antisense transcript, allowing the UBE3A gene to be expressed.

Advantages and Drawbacks

Both artificial transcription factors and antisense oligonucleotide therapy have shown promise in reactivating the UBE3A gene and rescuing phenotypes in mouse models of Angelman syndrome. However, it is challenging to summarize the advantages and drawbacks of each approach in a simple manner. Factors such as stability, administration methods, and the spectrum of phenotypes that can be rescued need to be considered. It is important to explore all promising approaches and determine the best course of action based on thorough analysis and consensus among researchers.

Conclusion

Gene expression is a complex process that plays a crucial role in determining the function of our cells. Understanding the mechanisms behind gene regulation opens up possibilities for therapeutic interventions. Both artificial transcription factors and antisense oligonucleotide therapy offer potential solutions for reactivating silenced genes, such as UBE3A in Angelman syndrome. Ongoing research and collaboration among scientists will help determine the most effective approach for treating genetic disorders and improving the lives of affected individuals.