The research was led by Dr Irène Amblard and Dr Vicki Metzis from the Development and Transcriptional Control group, in collaboration with LMS facilities and the Chromatin and Development and Computational Regulatory Genomics groups.
All cells contain the same DNA but must turn specific genes 'on' and 'off' – a process known as gene expression – to create different body parts. The cells in your eyes and arms harbour the same genes but 'express' them differently to become each body part. The work focused on the gene Cdx2. The duration of Cdx2 expression helps to determine where and when a cell produces spinal cord progenitors. The researchers wanted to understand what processes control this brief window.
The team discovered a DNA element they termed an 'attenuator', which reduces gene expression in a time and cell type-specific manner – unlike enhancers or silencers, other types of DNA elements that broadly switch genes on or off. By altering this element, they could tune how long or how strongly Cdx2 was expressed, effectively acting like a 'genetic dimmer switch'. Disrupting the 'switch' in mouse embryos also confirmed its essential role in shaping the developing body plan.
This breakthrough paves the way towards programmable gene expression, offering the ability to precisely control gene activity in space and time. The findings not only deepen our understanding of developmental biology but may inform new therapeutic strategies targeting the non-coding genome . Such approaches could one day enable treatments that selectively adjust gene expression in specific tissues, with implications for diseases caused by gene misregulation.
Vicki emphasized the potential: "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 a growing body of work exploring how non-coding DNA governs gene regulation – an area with profound implications for medicine, from designing new gene therapies to improving treatments.
