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Genes Dev 2005 Jul 15;1914:1723-34. doi: 10.1101/gad.1319105.
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Geminin regulates neuronal differentiation by antagonizing Brg1 activity.

Seo S , Herr A , Lim JW , Richardson GA , Richardson H , Kroll KL .

Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state.

PubMed ID: 16024661
PMC ID: PMC1176010
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cdt1 dll1 gal.2 gem gmnn myc ncam1 neurod1 neurod2 neurog1 neurog2 smarca4 sox2 sox3 tbrg1 tubb2b
Morpholinos: gmnn MO1 smarca4 MO1

Article Images: [+] show captions
References [+] :
Bain, Embryonic stem cells express neuronal properties in vitro. 1995, Pubmed