The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program
Open accessAbstract
The epigenome changes that underlie cellular differentiation in developing organisms are poorly understood. To gain insights into how pancreatic beta-cells are programmed, we profiled key histone methylations and transcripts in embryonic stem cells, multipotent progenitors of the nascent embryonic pancreas, purified beta-cells, and 10 differentiated tissues. We report that despite their endodermal origin, beta-cells show a transcriptional and active chromatin signature that is most similar to ectoderm-derived neural tissues. In contrast, the beta-cell signature of trimethylated H3K27, a mark of Polycomb-mediated repression, clusters with pancreatic progenitors, acinar cells and liver, consistent with the epigenetic transmission of this mark from endoderm progenitors to their differentiated cellular progeny. We also identified two H3K27 methylation events that arise in the beta-cell lineage after the pancreatic progenitor stage. One is a wave of cell-selective de novo H3K27 trimethylation in non-CpG island genes. Another is the loss of bivalent and H3K27me3-repressed chromatin in a core program of neural developmental regulators that enables a convergence of the gene activity state of beta-cells with that of neural cells. These findings reveal a dynamic regulation of Polycomb repression programs that shape the identity of differentiated beta-cells.
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Cites
High-Resolution Profiling of Histone Methylations in the Human Genome
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A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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Genome-scale DNA methylation maps of pluripotent and differentiated cells
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BackgroundThe β-globin nuclear compartment in development and erythroid differentiation
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Cited by
A DNA methylation atlas of normal human cell types
Loyfer, N., Magenheim, J., Peretz, A., Cann, G., Bredno, J., Klochendler, A., Fox-Fisher, I., Shabi-Porat, S., Hecht, M., Pelet, T., et al. (2023) · Nature · doi:10.1038/s41586-022-05580-6 · Cited by 656
Roles and regulation of histone methylation in animal development
Jambhekar, A., Dhall, A., & Shi, Y. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0151-1 · Cited by 556
Morán, I., Akerman, İ., van de Bunt, M., Xie, R., Benazra, M., Nammo, T., Arnes, L., Nakić, N., García-Hurtado, J., Rodríguez-Seguí, S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.010 · Cited by 447
Self-citationTranscriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Gifford, C. A., Ziller, M. J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A. K., Kelley, D. R., Shishkin, A. A., Issner, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.037 · Cited by 435
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351
Metadata
- Authors
- van Arensbergen, J., García-Hurtado, J., Moran, I., Maestro, M. A., Xu, X., Van de Casteele, M., Skoudy, A. L., Palassini, M., Heimberg, H., & Ferrer, J.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-04-15
- Volume
- 20
- Issue
- 6
- Pages
- 722-732
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W2047961180
- Cited by
- 161
- References
- 6
- Type
- posted content
- Language
- en
- Open access
- bronze
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- van Arensbergen, J., García-Hurtado, J., Moran, I., Maestro, M. A., Xu, X., Van de Casteele, M., Skoudy, A. L., Palassini, M., Heimberg, H., & Ferrer, J. (2010). Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program. Genome Research. https://doi.org/10.1101/gr.101709.109
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