Document Detail


Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.
MedLine Citation:
PMID:  21300881     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, during neural fate acquisition from mouse embryonic stem (ES) cells. Whereas Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminin's activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.
Authors:
Dhananjay Yellajoshyula; Ethan S Patterson; Matthew S Elitt; Kristen L Kroll
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-07
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-03-03     Completed Date:  2011-05-06     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3294-9     Citation Subset:  IM    
Affiliation:
Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE25737
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Animals
Cell Cycle Proteins / physiology*
Chromatin / chemistry
Embryonic Stem Cells / cytology*
Histones / metabolism
Mice
Nervous System / cytology,  growth & development*
Nuclear Proteins / physiology*
Pluripotent Stem Cells / cytology
Grant Support
ID/Acronym/Agency:
GM66815/GM/NIGMS NIH HHS; R01 GM066815-09/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Chromatin; 0/Gmnn protein, mouse; 0/Histones; 0/Nuclear Proteins
Comments/Corrections

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