A recent study has revealed that transcription factors find and activate their target genes by recognising how DNA is packaged inside the nucleus of cells, which could improve the effectiveness of converting one cell type into another – a grand challenge for regenerative medicine. This research may also help to understand how diseases such as cancer arise when the wrong genes are activated. In this study, we revealed how different groups of transcription factors can work together to decode the genome and change cells from one type to another. We believe that the guided-search model presented in our study can be applied to multiple physiological contexts and could have major impact for regenerative medicine. Dr Abdenour Soufi Centre for Regenerative Medicine & School of Biological Sciences Cellular reprogramming Cellular reprogramming, the process of converting one cell type to another, is a powerful technology with huge potential for healthcare and rejuvenation. The human body is made up of many different types of cells, which all begin as stem cells sharing the same genes, but can develop into different cell types by switching on specific sets of genes. This is controlled by proteins called transcription factors. Transcription factors can be used to reprogram cells in the lab. For example, scientists can convert adult skin cells back into stem cells, which can then be converted into different adult cell types. These reprogrammed cells could one day be used to replace or repair damaged tissues, such as heart muscle after a heart attack or neurons lost in dementia. Turning an adult cell back into a stem cell is relatively simple in the lab, and requires only four transcription factors. However, the process is inefficient and can lack specificity, which makes it challenging for clinical use. Dr Abdenour Soufi DNA signposts A key obstacle is understanding how those four transcription factors search for and identify their target genes. In this study, researchers found that these four transcription factors recognise unique directional DNA structures, which act like signposts to point the way to their target genes. When those structures are reversed, the transcription factors are guided to the wrong location, transcribing the wrong gene. This novel deep understanding could have implications for regenerative medicine by providing a more precise way to convert one cell type into another. Dr Abdenour Soufi did his PhD studying the embryonic transcription factor Hex/PRH at the University of Bristol (UK). He then moved to Prof Kenneth Zareth laboratory at the University of Pennsylvania (USA) where he performed seminal work on the Yamanaka transcription factors during cellular reprogramming to induced pluripotent stem (iPS) cells. In 2015, Abdenour established his lab at the Centre for Regenerative Medicine at the University of Edinburgh where he is now a senior lecturer. His research is focussed on revealing how transcription factors interact with chromatin and define cellular identity. The work was funded by the MRC, The University of Edinburgh Darwin Trust and Cancer Research UK. Nature paper Soufi Research Group Tags CRM Publication date 18 Dec, 2024
