Document Detail

Mof (MYST1 or KAT8) is essential for progression of embryonic development past the blastocyst stage and required for normal chromatin architecture.
MedLine Citation:
PMID:  18541669     Owner:  NLM     Status:  MEDLINE    
Acetylation of histone tails is a hallmark of transcriptionally active chromatin. Mof (males absent on the first; also called MYST1 or KAT8) is a member of the MYST family of histone acetyltransferases and was originally discovered as an essential component of the X chromosome dosage compensation system in Drosophila. In order to examine the role of Mof in mammals in vivo, we generated mice carrying a null mutation of the Mof gene. All Mof-deficient embryos fail to develop beyond the expanded blastocyst stage and die at implantation in vivo. Mof-deficient cell lines cannot be derived from Mof(-/-) embryos in vitro. Mof(-/-) embryos fail to acetylate histone 4 lysine 16 (H4K16) but have normal acetylation of other N-terminal histone lysine residues. Mof(-/-) cell nuclei exhibit abnormal chromatin aggregation preceding activation of caspase 3 and DNA fragmentation. We conclude that Mof is functionally nonredundant with the closely related MYST histone acetyltransferase Tip60. Our results show that Mof performs a different role in mammals from that in flies at the organism level, although the molecular function is conserved. We demonstrate that Mof is required specifically for the maintenance of H4K16 acetylation and normal chromatin architecture of all cells of early male and female embryos.
Tim Thomas; Mathew P Dixon; Andrew J Kueh; Anne K Voss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-09
Journal Detail:
Title:  Molecular and cellular biology     Volume:  28     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2008-08-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5093-105     Citation Subset:  IM    
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
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MeSH Terms
Blastocyst / metabolism*
Caspase 3 / metabolism
Cell Count
Cell Culture Techniques
Cell Survival
Chromatin / chemistry*
Embryo Loss
Embryo, Mammalian / enzymology,  pathology
Embryonic Development*
Enzyme Activation
Histone Acetyltransferases / metabolism*
Histones / metabolism
Lysine / metabolism
Mice, Inbred BALB C
Mutation / genetics
Reg. No./Substance:
0/Chromatin; 0/Histones; 56-87-1/Lysine; EC Acetyltransferases; EC protein, mouse; EC 3.4.22.-/Caspase 3

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