1. HBO1(KAT7) does not have an essential role in cell proliferation, DNA replication or histone 4 acetylation in human cells.
- Author
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Kueh, Andrew J., Eccles, Samantha, Tang, Leonie, Garnham, Alexandra L., May, Rose E., Herald, Marco J., Smyth, Gordon K., Voss, Anne K., and Thomas, Tim
- Subjects
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DNA replication , *HISTONE acetylation , *CELL proliferation , *DELETION mutation , *HELA cells , *HISTONES - Abstract
HBO1 (MYST2/KAT7) is essential for histone 3 lysine 14 acetylation (H3K14ac), but is dispensable for H4 acetylation and DNA replication in mouse tissues. In contrast, previous studies using siRNA knockdown in human cell lines have suggested that HBO1 is essential for DNA replication. To determine if HBO1 has distinctly different roles in immortalized human cell lines compared to normal mouse cells, we performed siRNA knockdown of HBO1. In addition, we used CRISPR/Cas9 to generate 293T, MCF7 and HeLa cell lines lacking HBO1. Using both techniques, we show that HBO1 is essential for all H3K14ac in human cells and is unlikely to have a direct effect on H4 acetylation and only minor effects on cell proliferation. Surprisingly, loss of HBO1 and H3K14ac in HeLa cells led to the secondary loss of almost all H4 acetylation after 4 weeks. Thus, HBO1 is dispensable for DNA replication and cell proliferation in immortalized human cells. However, while cell proliferation proceeded without HBO1 and H3K14ac, HBO1 gene deletion lead to profound changes in cell adhesion, particularly in 293T cells. Consistent with this phenotype, loss of HBO1 in both 293T and HeLa principally affected genes mediating cell adhesion with comparatively minor effects on other cellular processes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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