CRM scientists have identified the active genetic elements (enhancers) which control gene expression in human embryonic stem cells.
Embryonic stem cells have the capacity to change their cell identity to become any cell type in the body. Cell identity is controlled by transcription factors (TFs) which bind to enhancers to control which genes are switched on and off.
This study searches out active enhancers specific to human embryonic stem cells from across the human genome by combining two techniques. The first step is the purification of DNA segments boud by embryonic stem cell-specific Transcription Factors. The second step is an assay in which active enhancers switch on an artificial gene that turns cells green. The green cells can then be selected and the enhancers sequenced.
To date techniques to identify active enhancers have largely focussed on putative DNA segments rather than taking a more unbiased approach.
Prof Ian Chambers who led the study team said
"Using this approach helps us understand how cell identity is controlled by transcription factors. It has allowed us to identify a group of enhancers involved in maintaining embryonic stem cell identity."
This study was conducted in collaboration with groups in the Netherlands, Austria and Germany and is published in Cell Stem Cell. It was supported by funding from the Medical Research Council (UK) and the Wellcome Trust, and fellowships from Niels Stensen, EMBO (EMBOLTF) and Marie Sklodowska-Curie.
Barakat et al. (2018). Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells. Cell Stem Cell 23, 276–288, August 2, 2018 https://doi.org/10.1016/j.stem.2018.06.014