Cited by 175Genomics and Chromatin DynamicsPluripotent Stem Cells ResearchEpigenetics and DNA Methylation

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

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Tee, Wee-Wei, Shen, Steven S., Oksuz, Ozgur, Narendra, Varun, Reinberg, Danny·2014·Cell

DOI 10.1016/j.cell.2014.01.009PMC PMC4006806

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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.

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Authors: Tee, W.-W., Shen, S. S., Oksuz, O., Narendra, V., & Reinberg, D.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Reinberg, Danny
ORCID: Tee, Wee-Wei
Oksuz, Ozgur
Narendra, Varun
Reinberg, Danny
Venue: Cell
Publisher: Elsevier BV
Published: 2014-02
Volume: 156
Issue: 4
Pages: 678-690
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.01.009
PMC: PMC4006806
OpenAlex: W2058890095
Cited by: 165
References: 85
Citations by year: 2026: 6 · 2025: 7 · 2024: 10 · 2023: 15 · 2022: 11 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 8 · 2017: 20 · 2016: 21 · 2015: 21 · 2014: 8
FWCI: 9.57
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
New York Stem Cell Foundation
National Institutes of Health
National Cancer Institute (P30CA016087)
National Institute of General Medical Sciences (T32GM007308, R01GM037120, R01GM064844)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords: ERK signaling, mouse embryonic stem cells, pluripotency, chromatin, polycomb repressive complex 2, JARID2, nucleosome occupancy, TFIIH, developmental gene expression, transcriptional regulation
MeSH terms: Animals, Chromatin, Enzyme Activation, Nucleosomes, Phosphorylation, Promoter Regions, Genetic, RNA Polymerase II, Gene Expression Regulation, Developmental, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mice, Transcription Factor TFIIH, Embryonic Stem Cells, Polycomb Repressive Complex 2

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

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