Unknown,Transcriptomics,Genomics,Proteomics

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Chip-Seq of mouse Ago-1 and TRIM32-bound small RNAs from E14.5 brain.


ABSTRACT: In the mouse neocortex, neural progenitor cells generate neurons through repeated rounds of asymmetric cell division. How distinct fates are established in their daughter cells is unclear. We show here that the TRIM-NHL protein TRIM32 segregates asymmetrically during progenitor division and induces neuronal differentiation in one of the two daughter cells. TRIM32 is highly expressed in differentiating neurons. In both horizontally and vertically dividing progenitor cells, TRIM32 distribution becomes polarized in mitosis so that the protein is enriched in one of the two daughter cells. While TRIM32 overexpression induces cell cycle exit and neuronal differentiation, TRIM32 RNAi causes both daughter cells to proliferate and prevents the initiation of a neuronal differentiation program . TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific micro-RNAs. We show that Let-7 is one of the TRIM32 targets and is required and sufficient for neuronal differentiation. Our data suggest that the asymmetric segregation of a micro RNA regulator controls self renewal in the mammalian brain. Experiment Overall Design: small RNA from total mouse brain, Ago-1 and TRIM32 IPs were cloned and sequenced using 454 GS FLX system.

ORGANISM(S): Mus musculus

SUBMITTER: Eugene Berezikov 

PROVIDER: E-GEOD-12633 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors.

Schwamborn Jens C JC   Berezikov Eugene E   Knoblich Juergen A JA  

Cell 20090301 5


In the mouse neocortex, neural progenitor cells generate both differentiating neurons and daughter cells that maintain progenitor fate. Here, we show that the TRIM-NHL protein TRIM32 regulates protein degradation and microRNA activity to control the balance between those two daughter cell types. In both horizontally and vertically dividing progenitors, TRIM32 becomes polarized in mitosis and is concentrated in one of the two daughter cells. TRIM32 overexpression induces neuronal differentiation  ...[more]

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