Abstract
Erk1/2 activation contributes to mouse ES cell pluripotency. We found a direct role of Erk1/2 in modulating chromatin features required for regulated developmental gene expression. Erk2 binds to specific DNA sequence motifs typically accessed by Jarid2 and PRC2. Negating Erk1/2 activation leads to increased nucleosome occupancy and decreased occupancy of PRC2 and poised RNAPII at Erk2-PRC2-targeted developmental genes. Surprisingly, Erk2-PRC2-targeted genes are specifically devoid of TFIIH, known to phosphorylate RNA polymerase II (RNAPII) at serine-5, giving rise to its initiated form. Erk2 interacts with and phosphorylates RNAPII at its serine 5 residue, which is consistent with the presence of poised RNAPII as a function of Erk1/2 activation. These findings underscore a key role for Erk1/2 activation in promoting the primed status of developmental genes in mouse ES cells and suggest that the transcription complex at developmental genes is different than the complexes formed at other genes, offering alternative pathways of regulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 678-690 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 156 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 13 2014 |
Bibliographical note
Funding Information:We thank the Genome Technology Center at NYU for help with sequencing, Theodoros Savvidis for technical support, Jinsook Son and Dr. Shuzo Kaneko for reagents, and Drs. Lynne Vales, Philipp Voigt, and Roberto Bonasio for comments on the manuscript. We thank Drs. Yang Shi and Kristian Helin for kind gifts of the Jmjd3 and Utx antibodies, respectively. This work was supported by grants from the National Institutes of Health (GM-64844 and R37-37120), NYSTEM (C028105), and the Howard Hughes Medical Institute (to D.R.). W.-W.T. is a New York Stem Cell Foundation Druckenmiller Fellow. This research was supported by The New York Stem Cell Foundation (to W.-W.T.).
