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Cited by 451

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex

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Pereira, João D., Sansom, Stephen N., Smith, James, Dobenecker, Marc-Werner, Tarakhovsky, Alexander, Livesey, Frederick J.·2010·Proceedings of the National Academy of Sciences

Abstract

Multipotent progenitor cells of the cerebral cortex balance self-renewal and differentiation to produce complex neural lineages in a fixed temporal order in a cell-autonomous manner. We studied the role of the polycomb epigenetic system, a chromatin-based repressive mechanism, in controlling cortical progenitor cell self-renewal and differentiation. We found that the histone methyltransferase of polycomb repressive complex 2 (PCR2), enhancer of Zeste homolog 2 (Ezh2), is essential for controlling the rate at which development progresses within cortical progenitor cell lineages. Loss of function of Ezh2 removes the repressive mark of trimethylated histone H3 at lysine 27 (H3K27me3) in cortical progenitor cells and also prevents its establishment in postmitotic neurons. Removal of this repressive chromatin modification results in marked up-regulation in gene expression, the consequence of which is a shift in the balance between self-renewal and differentiation toward differentiation, both directly to neurons and indirectly via basal progenitor cell genesis. Although the temporal order of neurogenesis and gliogenesis are broadly conserved under these conditions, the timing of neurogenesis, the relative numbers of different cell types, and the switch to gliogenesis are all altered, narrowing the neurogenic period for progenitor cells and reducing their neuronal output. As a consequence, the timing of cortical development is altered significantly after loss of PRC2 function.

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Crossref · 10.1073/pnas.1002530107

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Metadata

Authors
Pereira, J. D., Sansom, S. N., Smith, J., Dobenecker, M.-W., Tarakhovsky, A., & Livesey, F. J.
Venue
Proceedings of the National Academy of Sciences
Published
2010-08-23
Volume
107
Issue
36
Pages
15957-15962
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2140815401
Cited by
451
References
9
FWCI
6.68
Type
journal article
Language
en
Open access
green

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