Histone acetyltransferase Hbo1: Catalytic activity, cellular abundance, and links to primary cancers

• Published in: Gene 2009-05, Vol.436 (1), p.108-114
• Main Authors: Iizuka, Masayoshi, Takahashi, Yoshihisa, Mizzen, Craig A., Cook, Richard G., Fujita, Masatoshi, Allis, C. David, Frierson, Henry F., Fukusato, Toshio, Smith, M. Mitchell
• Format: Article
• Language: English
• Subjects: Acetylation; Binding Sites; Blotting, Western; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Catalysis; Catalytic Domain; Cell Line; Cell Line, Tumor; Chromatin; DNA replication; Electrophoresis, Polyacrylamide Gel; Female; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histones - metabolism; Humans; Immunohistochemistry; Kidney Neoplasms - enzymology; Kidney Neoplasms - pathology; Licensing; Lysine - metabolism; Male; Neoplasms - enzymology; Neoplasms - pathology; Nucleosomes - metabolism; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - pathology; Proliferation; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Recombinant Proteins - metabolism; Schizosaccharomyces pombe; Tissue Array Analysis; Urinary Bladder Neoplasms - enzymology; Urinary Bladder Neoplasms - pathology
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2009.01.020

In addition to the well-characterized proteins that comprise the pre-replicative complex, recent studies suggest that chromatin structure plays an important role in DNA replication initiation. One of these chromatin factors is the histone acetyltransferase (HAT) Hbo1 which is unique among HAT enzymes in that it serves as a positive regulator of DNA replication. However, several of the basic properties of Hbo1 have not been previously examined, including its intrinsic catalytic activity, its molecular abundance in cells, and its pattern of expression in primary cancer cells. Here we show that recombinant Hbo1 can acetylate nucleosomal histone H4 in vitro, with a preference for lysines 5 and 12. Using semi-quantitative western blot analysis, we find that Hbo1 is approximately equimolar with the number of active replication origins in normal human fibroblasts but is an order of magnitude more abundant in both MCF7 and Saos-2 established cancer cell lines. Immunohistochemistry for Hbo1 in 11 primary human tumor types revealed strong Hbo1 protein expression in carcinomas of the testis, ovary, breast, stomach/esophagus, and bladder.