Here, he will discuss our recent work analysing epigenetic changes during the establishment and development of the human germline. Using a recently established stem cell model recapitulating linage segregation in the human embryo, we find that morphogen-induced enhancer remodelling defines a window of opportunity for germline specification during gastrulation. Here, the combinatorial function of mesendoderm transcription factors and BMP-SMAD signalling activates a transcription factor circuitry establishing the germ cell identity. Analysing epigenetic remodelling in first trimester human embryonic germ cells, we find a profound reduction of repressive epigenetic marks at most somatic genes and transposable elements (TEs) without transcriptional activation. Efficient maintenance of a heterochromatic state is limited to a subset of genomic loci, such as evolutionarily young TEs and some developmental genes. Accordingly, transcriptional repression in the early human germline presents an exemplary balanced system relying on local maintenance of heterochromatic features and a lack of inductive cues.

Biography: Dr Wolfram Gruhn is a postdoctoral research associate in Professor Azim Surani’s research group at the Gurdon institute in Cambridge. His research is focused on understanding the establishment and embryonic development of the mammalian germline. Here, he is particularly interested in the transcription factor-mediated regulation of cis-regulatory elements and the impact of epigenetic remodelling on transcription during human germ cell differentiation. To facilitate the study of transcription factor and cis-regulatory element function, Dr. Gruhn has contributed to the improvement of techniques such as mammalian DamID, auxin-inducible degrons, and CRISPR-mediated epigenome editing. His work has been supported by an EMBO long-term fellowship and the Eric Reid Fund for Methodology