HBO1 Is Required for H3K14 Acetylation and Normal Transcriptional Activity during Embryonic Development

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Molecular and Cellular Biology (Impact Factor: 4.78). 02/2011; 31(4):845-60. DOI: 10.1128/MCB.00159-10
Source: PubMed


We report here that the MYST histone acetyltransferase HBO1 (histone acetyltransferase bound to ORC; MYST2/KAT7) is essential for postgastrulation mammalian development. Lack of HBO1 led to a more than 90% reduction of
histone 3 lysine 14 (H3K14) acetylation, whereas no reduction of acetylation was detected at other histone residues. The decrease
in H3K14 acetylation was accompanied by a decrease in expression of the majority of genes studied. However, some genes, in
particular genes regulating embryonic patterning, were more severely affected than “housekeeping” genes. Development of HBO1-deficient
embryos was arrested at the 10-somite stage. Blood vessels, mesenchyme, and somites were disorganized. In contrast to previous
studies that reported cell cycle arrest in HBO1-depleted cultured cells, no defects in DNA replication or cell proliferation
were seen in Hbo1 mutant embryo primary fibroblasts or immortalized fibroblasts. Rather, a high rate of cell death and DNA fragmentation was
observed in Hbo1 mutant embryos, resulting initially in the degeneration of mesenchymal tissues and ultimately in embryonic lethality. In
conclusion, the primary role of HBO1 in development is that of a transcriptional activator, which is indispensable for H3K14
acetylation and for the normal expression of essential genes regulating embryonic development.

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Article: HBO1 Is Required for H3K14 Acetylation and Normal Transcriptional Activity during Embryonic Development

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