Document Detail

In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development.
MedLine Citation:
PMID:  21300888     Owner:  NLM     Status:  MEDLINE    
The proneural, basic helix-loop-helix transcription factor Atoh1 governs the development of numerous key neuronal subtypes, such as cerebellar granule and brainstem neurons, inner ear hair cells, and several neurons of the proprioceptive system, as well as diverse nonneuronal cell types, such as Merkel cells and intestinal secretory lineages. However, the mere handful of targets that have been identified barely begin to account for Atoh1's astonishing range of functions, which also encompasses seemingly paradoxical activities, such as promoting cell proliferation and medulloblastoma formation in the cerebellum and inducing cell cycle exit and suppressing tumorigenesis in the intestine. We used a multipronged approach to create a comprehensive, unbiased list of over 600 direct Atoh1 target genes in the postnatal cerebellum. We found that Atoh1 binds to a 10 nucleotide motif (AtEAM) to directly regulate genes involved in migration, cell adhesion, metabolism, and other previously unsuspected functions. This study expands current thinking about the transcriptional activities driving neuronal differentiation and provides a framework for further neurodevelopmental studies.
Tiemo J Klisch; Yuanxin Xi; Adriano Flora; Liguo Wang; Wei Li; Huda Y Zoghbi
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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:  3288-93     Citation Subset:  IM    
Department of Molecular and Human Genetics, The Howard Hughes Medical Institute, The Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
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MeSH Terms
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics,  physiology*
Binding Sites
Cell Differentiation
Cerebellum / growth & development*
Neurons / cytology*
Protein Binding
Transcription Factors / physiology
Grant Support
HD024064/HD/NICHD NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Atoh1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Transcription Factors

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

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