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XB-ART-45362
PLoS One January 1, 2012; 7 (5): e38009.

Geminin is required for zygotic gene expression at the Xenopus mid-blastula transition.

Kerns SL , Schultz KM , Barry KA , Thorne TM , McGarry TJ .


Abstract
In many organisms early development is under control of the maternal genome and zygotic gene expression is delayed until the mid-blastula transition (MBT). As zygotic transcription initiates, cell cycle checkpoints become activated and the tempo of cell division slows. The mechanisms that activate zygotic transcription at the MBT are incompletely understood, but they are of interest because they may resemble mechanisms that cause stem cells to stop dividing and terminally differentiate. The unstable regulatory protein Geminin is thought to coordinate cell division with cell differentiation. Geminin is a bi-functional protein. It prevents a second round of DNA replication during S and G2 phase by binding and inhibiting the essential replication factor Cdt1. Geminin also binds and inhibits a number of transcription factors and chromatin remodeling proteins and is thought to keep dividing cells in an undifferentiated state. We previously found that the cells of Geminin-deficient Xenopus embryos arrest in G2 phase just after the MBT then disintegrate at the onset of gastrulation. Here we report that they also fail to express most zygotic genes. The gene expression defect is cell-autonomous and is reproduced by over-expressing Cdt1 or by incubating the embryos in hydroxyurea. Geminin deficient and hydroxyurea-treated blastomeres accumulate DNA damage in the form of double stranded breaks. Bypassing the Chk1 pathway overcomes the cell cycle arrest caused by Geminin depletion but does not restore zygotic gene expression. In fact, bypassing the Chk1 pathway by itself induces double stranded breaks and abolishes zygotic transcription. We did not find evidence that Geminin has a replication-independent effect on transcription. We conclude that Geminin is required to maintain genome integrity during the rapid cleavage divisions, and that DNA damage disrupts zygotic gene transcription at the MBT, probably through activation of DNA damage checkpoint pathways.

PubMed ID: 22662261
PMC ID: PMC3360639
Article link: PLoS One

Genes referenced: ccnb1 cdk1 cdt1 chek1 chek2 gal.1 gal.2 gem gmnn gnl3 gsc h2ac21 h2axl inhba myc nodal5.2 nodal5.4 tbxt wnt8a zic3
Morpholinos: gmnn MO1 gmnn MO2


Article Images: [+] show captions
References [+] :
Benjamin, Geminin has dimerization, Cdt1-binding, and destruction domains that are required for biological activity. 2004, Pubmed, Xenbase


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