Eran Meshorer

Prof. Meshorer completed his PhD at the Hebrew University and performed his post-doctoral studies at the National Cancer Institute, NIH. In 2007 he returned to the Hebrew University as an Alon Fellow and is currently heading the Stem Cell Chromatin laboratory in the Department of Genetics and the Edmond and Lily Center for Brain Sciences (ELSC). Meshorer's research focuses on single cell and genome-wide approaches to understand chromatin plasticity and epigenetic regulation in embryonic and neuronal stem cells, during reprogramming, and in pluripotent models of neurodegenerative diseases. Prof. Meshorer is an ERC grant holder (2011), the winner of the Hestrin prize of the Israeli Society of Biochemistry and Molecular Biology (2012), the recipient of the Sir Zelman Cowen Award (2013) and the winner of the Vigevani Research Prize (2015).

 

Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify novel stem cell regulators, we generated a library of endogenously-labeled fluorescent fusion-proteins in mouse ESCs and screened for fluorescence loss during differentiation. We identified SET, which displayed rapid and significant isoform shift during early differentiation from the predominant isoform expressed in ESCs, SETα, to the primary isoform expressed in differentiated cell types, SETβ, through alternative promoters.

 

SETα is selectively bound and regulated by pluripotency factors. SET depletion causes proliferation slow-down and perturbed neuronal differentiation. Inducible expression of specific isoforms demonstrated that SETβ, but not SETα, is required for neuronal differentiation. Finally, photobleaching methods demonstrated SET's role in maintaining a dynamic chromatin state in ESCs. This work provides the first endogenously labeled fluorescent fusion protein library in ESCs, and identifies a novel regulator of pluripotency, proliferation and differentiation in mouse ESCs, controlled by alternative promoter usage.