Document Detail

Geminin restrains mesendodermal fate acquisition of embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced polycomb-mediated repression.
MedLine Citation:
PMID:  23630199     Owner:  NLM     Status:  MEDLINE    
Embryonic cells use both growth factor signaling and cell intrinsic transcriptional and epigenetic regulation to acquire early cell fates. Underlying mechanisms that integrate these cues are poorly understood. Here, we investigated the role of Geminin, a nucleoprotein that interacts with both transcription factors and epigenetic regulatory complexes, during fate acquisition of mouse embryonic stem cells. In order to determine Geminin's role in mesendoderm formation, a process which occurs during embryonic gastrulation, we selectively over-expressed or knocked down Geminin in an in vitro model of differentiating mouse embryonic stem cells. We found that Geminin antagonizes mesendodermal fate acquisition, while these cells instead maintain elevated expression of genes associated with pluripotency of embryonic stem cells. During mesendodermal fate acquisition, Geminin knockdown promotes Wnt signaling, while Bmp, Fgf, and Nodal signaling are not affected. Moreover, we showed that Geminin facilitates the repression of mesendodermal genes that are regulated by the Polycomb repressor complex. Geminin directly binds several of these genes, while Geminin knockdown in mesendodermal cells reduces Polycomb repressor complex occupancy at these loci and increases trimethylation of histone H3 lysine 4, which correlates with active gene expression. Together, these results indicate that Geminin is required to restrain mesendodermal fate acquisition of early embryonic cells and that this is associated with both decreased Wnt signaling and enhanced Polycomb repressor complex retention at mesendodermal genes.
Elizabeth A Caronna; Ethan S Patterson; Pamela M Hummert; Kristen L Kroll
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  31     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-09-16     Completed Date:  2014-06-15     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1477-87     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 AlphaMed Press.
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MeSH Terms
Cell Differentiation / physiology
Embryonic Stem Cells / cytology,  metabolism,  physiology*
Geminin / genetics,  metabolism,  physiology*
Gene Expression Regulation, Developmental
Mesoderm / cytology,  metabolism,  physiology*
Microarray Analysis
Polycomb-Group Proteins / genetics,  metabolism,  physiology*
Repressor Proteins / genetics,  metabolism
Wnt Signaling Pathway
Grant Support
Reg. No./Substance:
0/Geminin; 0/Polycomb-Group Proteins; 0/Repressor Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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