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Status |
Public on Sep 27, 2013 |
Title |
Miz1 is required to maintain autophagic flux |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Miz1 is a zinc finger protein that regulates expression of cell cycle inhibitors as part of a complex with Myc. Cell cycle-independent functions of Miz1 are poorly understood. Here, we use a Nestin-Cre transgene to delete an essential domain of Miz1 in the central nervous system (Miz1ΔPOZNes). Miz1ΔPOZNes mice display cerebellar neurodegeneration characterized by the progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and biochemical analyses show that Miz1 activates transcription upon binding to a non-palindromic sequence present in core promoters. Target genes of Miz1 encode regulators of autophagy and proteins involved in vesicular transport that are required for autophagy. Miz1ΔPOZ neuronal progenitors and fibroblasts show reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1 accumulate in the cerebella of Miz1ΔPOZNes mice, characteristic features of defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome biogenesis to the transcriptional regulation of vesicular transport and autophagy.
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Overall design |
ChIP-Seq with H190 and G18 on an Illumina Genome Analyzer IIx.
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Contributor(s) |
Wolf E, Gebhardt A, Kawauchi D, Walz S, von Eyss B, Wagner N, Renninger C, Krohne G, Asan E, Roussel M, Eilers M |
Citation(s) |
24088869 |
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Submission date |
Jul 08, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Martin Eilers |
Organization name |
University of Wuerzburg
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Department |
Chair for Biochemistry and Molecular Biology
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Lab |
Martin Eilers
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Street address |
Am Hubland
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City |
Wuerzburg |
ZIP/Postal code |
97074 |
Country |
Germany |
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Platforms (2) |
GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA210788 |
SRA |
SRP026622 |