Researchers from the Ludwig Maximilian University of Munich (LMU) made significant progress in unraveling novel mechanisms of glia-to-neuron conversion. By using novel methods in epigenome profiling, they identify a posttranslational modification of Neurogenin2 which profoundly impacts epigenetic rewiring and the improvement in neuronal programming. Specifically, they identified a novel protein as key player in this conversion process: the transcriptional regulator YingYang1. YingYang1 physically interacts with Neurogenin2 to open up the chromatin. Thus, these novel insights reveal how the conversion at the molecular level works and pave the way to improve the reprogramming of glial cells into neurons.
First, the researchers identified that the phosphorylation-resistant form of Neurogenin2 profoundly improved the epigenetic rewiring and neuronal reprogramming. Additionally, they found an essential transcriptional co-factor, YingYang1, to reprogram the glial cells into neurons. Yingyang1 is predominatly up-regualted by the phosphorylation-resistant form of Ngn2. YingYang1 is necessary to open up the chromatin for reprogramming, after which it interacts with the transcription factor. In summary, the protein is crucial for achieving the conversion from astrocytes to neurons.
Read the full press release here.
Read the full article here:
Pereira, A., Diwakar, J., Masserdotti, G. et al. Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1. published in Nature Neuroscience (2024). https://doi.org/10.1038/s41593-024-01677-5
Magdalena Götz is the project leader of project C05 in our consortium.
