Transcriptional control of pluripotent stem cell fate
Transcriptional control of pluripotent stem cell fate by the Nucleosome Remodelling and Deacetylation (NuRD) complex
Chromatin remodelling complexes play essential roles in metazoan development through widespread control of gene expression. The genetic requirements for many of the components of such complexes have been described, and their biochemical activities characterised in vitro, yet the precise molecular mechanisms by which chromatin remodellers impact transcriptional regulation in vivo remain ill-defined. In my lab we have been studying the Nucleosome Remodelling and Deacetylation (NuRD) complex in mouse ES cells. Functionally, NuRD is required for pluripotent cells to properly undergo lineage commitment both in vitro and in vivo, and mouse embryos lacking key NuRD components die in peri-implantation stages. Despite these profound developmental defects, NuRD deficiency in ES cells results in only moderate gene expression changes, with the majority of genes changing by less than two-fold. These small transcriptional changes nevertheless result in a profound phenotype of developmental failure. I will present or latest results in defining molecularly how the enzymatic activities of NuRD fine-tune transcription in mouse ES cells, and how biochemical dissection of NuRD can be used to define NuRD function during lineage commitment.
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