Advanced search
1 file | 3.27 MB

Integrative proteomic profiling reveals PRC2-dependent epigenetic crosstalk maintains ground-state pluripotency

(2019) CELL STEM CELL. 24(1). p.123-137
Author
Organization
Abstract
The pluripotent ground state is defined as a basal state free of epigenetic restrictions, which influence lineage specification. While naive embryonic stem cells (ESCs) can be maintained in a hypomethylated state with open chromatin when grown using two small-molecule inhibitors (2i)/leukemia inhibitory factor (LIF), in contrast to serum/LIF-grownESCs that resemble early post-implantation embryos, broader features of the ground-state pluripotent epigenome are not well understood. We identified epigenetic features of mouse ESCs cultured using 2i/LIF or serum/LIF by proteomic profiling of chromatin-associated complexes and histone modifications. Polycomb-repressive complex 2 (PRC2) and its product H3K27me3 are highly abundant in 2i/LIF ESCs, and H3K27me3 is distributed genome-wide in a CpG-dependent fashion. Consistently, PRC2-deficient ESCs showed increased DNA methylation at sites normally occupied by H3K27me3 and increased H4 acetylation. Inhibiting DNA methylation in PRC2-deficient ESCs did not affect their viability or transcriptome. Our findings suggest a unique H3K27me3 configuration protects naive ESCs from lineage priming, and they reveal widespread epigenetic crosstalk in ground-state pluripotency.
Keywords
EMBRYONIC STEM-CELLS, DNA METHYLATION, POLYCOMB, CHROMATIN, NAIVE, PRC2, MAINTENANCE, IDENTIFICATION, DEMETHYLATION, PROTEINS

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 3.27 MB

Citation

Please use this url to cite or link to this publication:

Chicago
van Mierlo, Guido, René AM Dirks, Laura De Clerck, Arie B Brinkman, Michelle Huth, Susan L Kloet, Nehmé Saksouk, et al. 2019. “Integrative Proteomic Profiling Reveals PRC2-dependent Epigenetic Crosstalk Maintains Ground-state Pluripotency.” Cell Stem Cell 24 (1): 123–137.
APA
van Mierlo, G., Dirks, R. A., De Clerck, L., Brinkman, A. B., Huth, M., Kloet, S. L., Saksouk, N., et al. (2019). Integrative proteomic profiling reveals PRC2-dependent epigenetic crosstalk maintains ground-state pluripotency. CELL STEM CELL, 24(1), 123–137.
Vancouver
1.
van Mierlo G, Dirks RA, De Clerck L, Brinkman AB, Huth M, Kloet SL, et al. Integrative proteomic profiling reveals PRC2-dependent epigenetic crosstalk maintains ground-state pluripotency. CELL STEM CELL. 2019;24(1):123–37.
MLA
van Mierlo, Guido et al. “Integrative Proteomic Profiling Reveals PRC2-dependent Epigenetic Crosstalk Maintains Ground-state Pluripotency.” CELL STEM CELL 24.1 (2019): 123–137. Print.
@article{8581872,
  abstract     = {The pluripotent ground state is defined as a basal state free of epigenetic restrictions, which influence lineage specification. While naive embryonic stem cells (ESCs) can be maintained in a hypomethylated state with open chromatin when grown using two small-molecule inhibitors (2i)/leukemia inhibitory factor (LIF), in contrast to serum/LIF-grownESCs that resemble early post-implantation embryos, broader features of the ground-state pluripotent epigenome are not well understood. We identified epigenetic features of mouse ESCs cultured using 2i/LIF or serum/LIF by proteomic profiling of chromatin-associated complexes and histone modifications. Polycomb-repressive complex 2 (PRC2) and its product H3K27me3 are highly abundant in 2i/LIF ESCs, and H3K27me3 is distributed genome-wide in a CpG-dependent fashion. Consistently, PRC2-deficient ESCs showed increased DNA methylation at sites normally occupied by H3K27me3 and increased H4 acetylation. Inhibiting DNA methylation in PRC2-deficient ESCs did not affect their viability or transcriptome. Our findings suggest a unique H3K27me3 configuration protects naive ESCs from lineage priming, and they reveal widespread epigenetic crosstalk in ground-state pluripotency.},
  author       = {van Mierlo, Guido and Dirks, Ren{\'e} AM and De Clerck, Laura and Brinkman, Arie B and Huth, Michelle and Kloet, Susan L and Saksouk, Nehm{\'e} and Kroeze, Leonie I and Willems, Sander and Farlik, Matthias and Bock, Christoph and Jansen, Joop H and Deforce, Dieter and Vermeulen, Michiel and D{\'e}jardin, J{\'e}r{\^o}me and Dhaenens, Maarten and Marks, Hendrik},
  issn         = {1934-5909},
  journal      = {CELL STEM CELL},
  language     = {eng},
  number       = {1},
  pages        = {123--137},
  title        = {Integrative proteomic profiling reveals PRC2-dependent epigenetic crosstalk maintains ground-state pluripotency},
  url          = {http://dx.doi.org/10.1016/j.stem.2018.10.017},
  volume       = {24},
  year         = {2019},
}

Altmetric
View in Altmetric
Web of Science
Times cited: