Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development

We report that while individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. We further show that Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for ESC maintenance, and increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity.

Source: EMBO Journal - July 14, 2016 Category: Molecular Biology Authors: Pedersen, M. T., Kooistra, S. M., Radzisheuskaya, A., Laugesen, A., Johansen, J. V., Hayward, D. G., Nilsson, J., Agger, K., Helin, K. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Stem Cells, Transcription Articles Source Type: research