title: Erk1/2 activity promotes chromatin features and RNAPII phosphorylation at developmental promoters in mouse ESCs.
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.
authors: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors: Wee-Wei
authors: WW
authors: Tee
authors: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY 10016, USA.
authors: Steven S
authors: SS
authors: Shen
authors: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors: Ozgur
authors: O
authors: Oksuz
authors: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors: Varun
authors: V
authors: Narendra
authors: Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: danny.reinberg@nyumc.org.
authors: Danny
authors: D
authors: Reinberg
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism*
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D051758:Transcription Factor TFIIH; D063151:Polycomb Repressive Complex 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D012319:RNA Polymerase II