title: Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908-0734, USA.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iizuka
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Craig A
authors.initials: CA
authors.lastname: Mizzen
authors.forename: Richard G
authors.initials: RG
authors.lastname: Cook
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.forename: Henry F
authors.initials: HF
authors.lastname: Frierson
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.forename: M Mitchell
authors.initials: MM
authors.lastname: Smith
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D002384:Catalysis; D020134:Catalytic Domain; D002460:Cell Line; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human; D008239:Lysine