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  MOF maintains transcriptional programs regulating cellular stress response

Sheikh, B., Bechtel-Walz, W., Lucci, J., Karpuik, O., Hild, I., Hartleben, B., et al. (2016). MOF maintains transcriptional programs regulating cellular stress response. Oncogene, 35, 2698-2710. doi:doi: 10.1038/onc.2015.335.

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Sheikh, B.N.1, Author
Bechtel-Walz, W.2, Author
Lucci, Jacopo3, Author              
Karpuik, O.1, Author
Hild, I.2, Author
Hartleben, B.2, Author
Vornweg, J.2, Author
Helmstädter, M.2, Author
Sahyoun, A.H.1, Author
Bhardwaj, V.1, Author
Stehle, Thomas4, Author              
Diehl, S.1, Author
Kretz, O.2, 5, Author
Voss, A.K.6, 7, Author
Thomas, T.6, 7, Author
Manke, Thomas8, Author              
Huber, T.B.2, 9, Author
Akhtar, Asifa3, Author              
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2Renal Division, University Medical Center, Freiburg, Germany, ou_persistent22              
3Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243643              
4Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243654              
5Neuroanatomy, University Freiburg, Freiburg, Germany, ou_persistent22              
6Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia, ou_persistent22              
7Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia, ou_persistent22              
8Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              
9BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University, Freiburg, Germany, ou_persistent22              

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 Abstract: MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.

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Language(s): eng - English
 Dates: 2016-05
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: doi: 10.1038/onc.2015.335
 Degree: -

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Title: Oncogene
Source Genre: Journal
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Publ. Info: Basingstoke, Hampshire, UK : Scientific & Medical Division, Macmillan Press
Pages: 13 Volume / Issue: 35 Sequence Number: - Start / End Page: 2698 - 2710 Identifier: ISSN: 0950-9232
Other: 954925574955
CoNE: https://pure.mpg.de/cone/journals/resource/954925574955