Document Detail


RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
MedLine Citation:
PMID:  22232429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pancreas development is initiated by the specification and expansion of a small group of endodermal cells. Several transcription factors are crucial for progenitor maintenance and expansion, but their interactions and the downstream targets mediating their activity are poorly understood. Among those factors, PTF1a, a basic helix-loop-helix (bHLH) transcription factor which controls pancreas exocrine cell differentiation, maintenance, and functionality, is also needed for the early specification of pancreas progenitors. We used RNA profiling and chromatin immunoprecipitation (ChIP) sequencing to identify a set of targets in pancreas progenitors. We demonstrate that Mnx1, a gene that is absolutely required in pancreas progenitors, is a major direct target of PTF1a and is regulated by a distant enhancer element. Pdx1, Nkx6.1, and Onecut1 are also direct PTF1a targets whose expression is promoted by PTF1a. These proteins, most of which were previously shown to be necessary for pancreas bud maintenance or formation, form a transcription factor network that allows the maintenance of pancreas progenitors. In addition, we identify Bmp7, Nr5a2, RhoV, and P2rx1 as new targets of PTF1a in pancreas progenitors.
Authors:
Nancy Thompson; Emilie Gésina; Peter Scheinert; Philipp Bucher; Anne Grapin-Botton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-09
Journal Detail:
Title:  Molecular and cellular biology     Volume:  32     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-23     Completed Date:  2012-04-13     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1189-99     Citation Subset:  IM    
Affiliation:
Swiss Institute for Experimental Cancer Researcha and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatin Immunoprecipitation*
Gene Expression Regulation, Developmental*
Homeodomain Proteins / genetics,  metabolism*
Mice
Mice, Knockout
Pancreas / cytology,  growth & development*,  metabolism
RNA / genetics*
Stem Cells / cytology,  metabolism*
Transcription Factors / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Transcription Factors; 0/transcription factor PTF1; 140115-73-7/Hb9 protein, mouse; 63231-63-0/RNA
Comments/Corrections

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