MOF maintains transcriptional programs regulating cellular stress response
Details
Publication Year 2015-09-21, Volume 35, Issue #21, Page 3451-3462
Journal Title
Oncogene
Publication Type
Journal Article
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.Oncogene advance online publication, 21 September 2015; doi:10.1038/onc.2015.335.
Publisher
NPG
WEHI Research Division(s)
Development And Cancer
PubMed ID
26387537
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-09-24 02:12:28
Last Modified: 2017-09-29 12:07:49
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