Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers.
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.
Iizuka
Masayoshi
M
Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908-0734, USA.
Takahashi
Yoshihisa
Y
Mizzen
Craig A
CA
Cook
Richard G
RG
Fujita
Masatoshi
M
Allis
C David
CD
Frierson
Henry F
HF
Fukusato
Toshio
T
Smith
M Mitchell
MM
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
D006657:Histones; D009707:Nucleosomes; D011994:Recombinant Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human; D008239:Lysine