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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    • "Error bars represent mean ±SD, n = 4. p-value of two-tailed Student's t-test is indicated.Chameau subfamily of the MYST family histone acetyltransferases has been mainly considered to function in an epigenetic mechanism of transcriptional repression since haploinsufficiency of Chameau leads to defects of position effect variegation[14]. Recently, it was also shown that Chameau cooperates with JNK signaling to promote transcriptional activation[15]and Hbo1, the human homologue of Chameau, is required for H3K14 acetylation and normal transcriptional activity during embryonic development[17]. These contradictory observations can be explained by either multiple targets or a co-regulator of Chameau. "
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    • "Analyzing the phosphoproteome of a collection of yeast kinase and phosphatase mutants, Aebersold and colleagues reported a similar number of gains and losses in phosphorylation sites across all mutants together (Bodenmiller et al., 2010). Voss and colleagues found that reduced levels of H3.K14ac in hbo1 knockout mice were accompanied by increases in H4.K16ac and to a lesser extent in H4.K5ac and H3.K9ac (Kueh et al., 2011). Ge and coworkers made similar findings for cbp/p300 double deletion lines, which displayed increased levels of H3.K23ac and H3.K9me1K14ac (Jin et al., 2011). "
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    • "HBO1, also known as MYST2 or KAT7, is a member of the MYST family of HATs. It is specifically required for H3K14ac in mammalian cells [34]. Another member of the MYST family of HATs, MOF (also known as MYST1 or KAT8), is specifically required for H4K16ac in mammalian cells [80]. "
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