Eric Bareke

Abstract H3K36 methylation is a key epigenetic mark with critical roles in development and disease. Here, we systematically dissect its functions using CRISPR-engineered mouse mesenchymal stem cells lacking combinations of the five H3K36 methyltransferases, culminating in quintuple knockout cells devoid of H3K36me2/3. We show that H3K36me2 influences enhancer activity, supports the expression of their target genes, and safeguards active genes from encroachment of the repressive marks, H3K27me2/3.

1Department of Human Genetics, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada 2Department of Obstetrics and Gynecology, Alexandria University, Egypt 3Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt 4State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Beijing Institute of Stem Cell and Regenerative Medicine, IOZ/CAS, University of Chinese...

Abstract NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3,4,5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable.