Document Detail


Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx.
MedLine Citation:
PMID:  21497756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adult pancreatic β cells can replicate during growth and after injury to maintain glucose homeostasis. Here, we report that β cells deficient in Dnmt1, an enzyme that propagates DNA methylation patterns during cell division, were converted to α cells. We identified the lineage determination gene aristaless-related homeobox (Arx), as methylated and repressed in β cells, and hypomethylated and expressed in α cells and Dnmt1-deficient β cells. We show that the methylated region of the Arx locus in β cells was bound by methyl-binding protein MeCP2, which recruited PRMT6, an enzyme that methylates histone H3R2 resulting in repression of Arx. This suggests that propagation of DNA methylation during cell division also ensures recruitment of enzymatic machinery capable of modifying and transmitting histone marks. Our results reveal that propagation of DNA methylation during cell division is essential for repression of α cell lineage determination genes to maintain pancreatic β cell identity.
Authors:
Sangeeta Dhawan; Senta Georgia; Shuen-Ing Tschen; Guoping Fan; Anil Bhushan
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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:  Developmental cell     Volume:  20     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-18     Completed Date:  2011-06-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-29     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-7073, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division
Cell Line
DNA (Cytosine-5-)-Methyltransferase / deficiency,  metabolism
DNA Methylation / genetics*
Genome-Wide Association Study
Homeodomain Proteins / genetics*,  metabolism
Insulin-Secreting Cells / cytology*,  metabolism*
Methyl-CpG-Binding Protein 2 / metabolism
Mice
Transcription Factors / deficiency*,  genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
DK068763/DK/NIDDK NIH HHS; DK080996/DK/NIDDK NIH HHS; DK089532/DK/NIDDK NIH HHS; K01 DK088995/DK/NIDDK NIH HHS; K01 DK088995-02/DK/NIDDK NIH HHS; R01 DK068763-08/DK/NIDDK NIH HHS; R01 DK080996-04/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/ARX protein, mouse; 0/Homeodomain Proteins; 0/Mecp2 protein, mouse; 0/Methyl-CpG-Binding Protein 2; 0/Transcription Factors; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1
Comments/Corrections
Comment In:
Dev Cell. 2011 Apr 19;20(4):411-2   [PMID:  21497752 ]

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


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