title: MOF maintains transcriptional programs regulating cellular stress response.
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.
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: B N
authors.initials: BN
authors.lastname: Sheikh
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Bechtel-Walz
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lucci
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Karpiuk
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Hild
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hartleben
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Vornweg
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Helmstädter
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: A H
authors.initials: AH
authors.lastname: Sahyoun
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Bhardwaj
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Stehle
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Diehl
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.|Neuroanatomy, University Freiburg, Freiburg im Breisgau, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Kretz
authors.affiliation: Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: A K
authors.initials: AK
authors.lastname: Voss
authors.affiliation: Development and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Manke
authors.affiliation: Renal Division, University Medical Center, Freiburg, Germany.|BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: T B
authors.initials: TB
authors.lastname: Huber
authors.affiliation: Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; C112525:SCARA3 protein, human; D051117:Scavenger Receptors, Class A; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C000622683:Kat8 protein, mouse