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The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF ‐16/ FOXO transcription factors
Author(s) -
Ikeda Takako,
Uno Masaharu,
Honjoh Sakiko,
Nishida Eisuke
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201743907
Subject(s) - histone acetyltransferase , acetylation , histone , histone deacetylase , biology , transcription factor , histone h4 , epigenetics , acetyltransferase , transcriptional regulation , caenorhabditis elegans , chromatin , hdac4 , microbiology and biotechnology , genetics , regulation of gene expression , creb binding protein , gene , creb
The well‐known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex ( MYS ‐1/ TRR ‐1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans . Our results show that these beneficial effects are largely mediated through transcriptional up‐regulation of the FOXO transcription factor DAF ‐16. MYS ‐1 and TRR ‐1 are recruited to the promoter regions of the daf‐16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/ TRRAP complex promotes oxidative stress resistance by up‐regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to the promoter regions of the foxo1 gene, where it increases H4K16 acetylation levels. Our results thus identify the evolutionarily conserved role of the MYST family acetyltransferase as a key epigenetic regulator of DAF ‐16/ FOXO transcription factors.