Determining the role of the protein demethylase, LSD1, in early tissue development

Chromatin modifying complexes are essential for the shift between heterochromatin and euchromatin, allowing repression and activation of genes. The importance of these complexes are particularly apparent in early development, where the epigenetic landscape changes significantly as cells progress from pluripotency to lineage commitment. LSD1, which forms part of the repressive CoREST complex, is a demethylase that has been shown to be essential in the differentiation of embryonic stem (ES) cells. LSD1 knockout ES cells show no change to proliferation but differentiation results in increased cell death and misexpression of both mesodermal and endodermal markers. To investigate the role of LSD1 in the differentiation of mesodermal/endodermal lineages, conditional Lsd1 knock out ES cells will be differentiated into mesoderm/endoderm and their transcriptome and LSD1 interactome investigated.