Unknown,Transcriptomics,Genomics,Proteomics

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The Atoh1 targetome in murine postnatal cerebellum


ABSTRACT: A relatively small number of proneural transcription factors specify a multitude of neural progenitor populations in the developing mammalian brain. Despite their importance, little is known about their targets, cellular processes they regulate, or what genomic sites they occupy in vivo. We used an integrated experimental and computational approach, combining RNA-seq, Histone-seq, and Atoh1 ChIP-seq in cerebellar tissue, to identify over 600 targets of Atoh1, an important developmental transcription factor. We validated 10% of these targets and found that Atoh1 directly regulates genes involved not only in early proliferation but also later differentiation, migration, cell adhesion, metabolism, and cytoskeletal organization by recognizing a novel 10 nucleotide Atoh1 E-Box associated motif (AtEAM). This Atoh1 “targetome” is not only a resource for studies aimed at understanding the molecular mechanisms involved in cerebellar development, but our integrated approach provides a framework for future in vivo studies of transcription factors and their targetomes. Examination of RNA-seq WT and null expression data (2 reps each), 2 different histone modifications (2 rep each) and IgG control, and Atoh1 DNA-binding (2 reps each) and control in the developing cerebellum

ORGANISM(S): Mus musculus

SUBMITTER: Yuanxin Xi 

PROVIDER: E-GEOD-22111 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Klisch Tiemo J TJ   Xi Yuanxin Y   Flora Adriano A   Wang Liguo L   Li Wei W   Zoghbi Huda Y HY  

Proceedings of the National Academy of Sciences of the United States of America 20110207 8


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 s  ...[more]

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