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

Kueh, AJ; Dixon, MP; Voss, AK; Thomas, T

Author(s): Kueh, AJ; Dixon, MP; Voss, AK; Thomas, T;
Details: Publication Year 2011-02,Volume 31,Issue #4,Page 845-860
Journal Title: MOLECULAR AND CELLULAR BIOLOGY
Publication Type: Journal Article
Abstract: 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.
Publisher: AMER SOC MICROBIOLOGY
Keywords: HISTONE ACETYLTRANSFERASE HBO1; RECEPTOR TYROSINE KINASE; HEMATOPOIETIC STEM-CELLS; LEUKEMIA ZINC-FINGER; GENE-CODING REGIONS; DNA-REPLICATION; ENDOTHELIAL-CELLS; MAMMALIAN-CELLS; MOUSE EMBRYO; IN-VITRO
Publisher's Version: https://doi.org/10.1128/MCB.00159-10
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-02-01 12:00:00