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Publication : In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development.

First Author  Klisch TJ Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  8 Pages  3288-93
PubMed ID  21300888 Mgi Jnum  J:169298
Mgi Id  MGI:4940414 Doi  10.1073/pnas.1100230108
Citation  Klisch TJ, et al. (2011) In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development. Proc Natl Acad Sci U S A 108(8):3288-93
abstractText  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.
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