Erk1/2 Activity Promotes Chromatin Features and RNAPII Phosphorylation at Developmental Promoters in Mouse ESCs

• Published in: Cell Vol. 156; no. 4; pp. 678 - 690
• Main Authors: Tee, Wee-Wei, Shen, Steven S., Oksuz, Ozgur, Narendra, Varun, Reinberg, Danny
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-02-2014
• Subjects: Animals; Chromatin - metabolism; Embryonic Stem Cells - metabolism; Enzyme Activation; Gene Expression Regulation, Developmental; Mice; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Nucleosomes - metabolism; Phosphorylation; Polycomb Repressive Complex 2 - metabolism; Promoter Regions, Genetic; RNA Polymerase II - metabolism; Transcription Factor TFIIH - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2014.01.009

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.
[Display omitted]
•Erk1/2 activity regulates the targeting of PRC2-Jarid2 in mouse ESCs•Erk2 binds to a cohort of PRC2-targeted developmental genes•Erk2 phosphorylates RNAPII at its serine 5 residue at developmental genes•TFIIH is present on active genes but is absent on Erk2-PRC2 developmental genes
The MAPK Erk1/2 has a direct role in the core transcriptional machinery at a specific set of genes in ESCs. Erk1/2 binds to specific DNA sequences to influence nucleosome occupancy and appears to substitute for the core transcription factor TFIIH to phosphorylate RNA polymerase II.