Scientists at the MRC Laboratory of Medical Sciences have identified a genetic 'dimmer switch' that controls how genes turn on and off during embryo formation, offering insights for future therapies.
A team of researchers at the MRC Laboratory of Medical Sciences (LMS) has uncovered a previously unknown mechanism that regulates gene activation and deactivation during embryonic development. Their findings, published in Developmental Cell, explain how diverse cell types emerge as an embryo forms.
The study was led by Dr. Irène Amblard and Dr. Vicki Metzis from the Development and Transcriptional Control group, in collaboration with other LMS facilities and research groups focusing on Chromatin and Development as well as Computational Regulatory Genomics.
Although all cells carry identical DNA, they must switch specific genes 'on' and 'off' – a process called gene expression – to become different tissues and organs. For example, cells in the eyes and arms contain the same genes but express them differently to form their unique structures.
The researchers focused on a gene known as Cdx2, which plays a critical role in producing spinal cord progenitors during development. They sought to understand what controls the timing of its expression, as this timing determines where and when these progenitor cells are formed.
The team discovered a previously unidentified DNA element that they termed an ‘attenuator’. Unlike enhancers or silencers that broadly activate or repress genes, this attenuator acts in a time- and cell type-specific way to reduce gene expression. Essentially, it functions like a ‘genetic dimmer switch’, fine-tuning how long or how strongly the Cdx2 gene is activated.
By altering this attenuator, researchers could adjust the duration and intensity of Cdx2 expression. Disrupting the element in mouse embryos confirmed its essential role in shaping the body plan during development.
This discovery paves the way towards programmable gene expression, offering the possibility of precise control over when and where genes are active. Such control could inform therapeutic strategies targeting non-coding regions of DNA, which may one day enable treatments that selectively adjust gene expression in specific tissues to correct diseases caused by gene misregulation.
Dr. Vicki Metzis emphasised the potential of this research, stating: "We're excited because previous research suggests that our genome may harbour many different types of elements that finely tune gene expression, but they've not been easy to identify. If we can address this challenge, this holds enormous potential for unlocking new ways to treat diseases by fine-tuning gene expression where and when it's needed."
The study, funded by Wellcome with support from the Medical Research Council, adds to growing research on how non-coding DNA governs gene regulation. This area of biology has profound implications for developing new gene therapies and improving existing treatments.
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