HBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells

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 small interfering RNA (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 and 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 has minor effects on cell proliferation. Surprisingly, the 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 led to profound changes in cell adhesion, particularly in 293T cells. Consistent with this phenotype, the loss of HBO1 in both 293T and HeLa principally affected genes mediating cell adhesion, with comparatively minor effects on other cellular processes.

A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer

“…Our dCypher and ChIP-seq experiments suggest that H3K4 methyl, H3K14ac, and H4K12ac nucleosomes serve as high-affinity PHIP binding sites, implying a concerted activity of COMPASS methyltransferases and lysine acetyltransferases, and understanding how this is coordinated will be an important area for future work. Potential candidates involved in recruiting PHIP to H3K14ac include GCN5 and HBO1, while HAT1 and NuA4 may mediate H4K12ac ( Roth et al 2001 ; Lee and Workman 2007 ; Kueh et al 2020 ).…”

The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma

“…While genetic silencing or pharmacological inhibition of HBO1 potently inhibited leukemia stem cell progression 33 . Kueh and colleagues, however, reported that HBO1 does not have an essential role in cell proliferation and DNA replication in HEK293T, MCF7, or HeLa 36 . In this study, we tested the expression and potential function of HBO1 in human OS 36 , and we show that overexpressed HBO1 acts as a novel oncogenic gene essential for OS cell tumorigenesis and progression.…”

The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver

“…This suggests that ING5 has a specific role in modulating the activity of chromatin regulatory complexes in which it is found. KAT7 has a global function in regulating H3K14ac ( 46 , 60 – 62 ), but under different conditions has been shown to acetylate H4 ( 26 ). KAT6A has a function in regulating H3K23ac ( 63 ) and H3K9ac at specific loci ( 64 – 67 ).…”