title: Transcription factor Runx1 recruits the polyomavirus replication origin to replication factories.
abstract: Eukaryotic DNA replication takes place in the replication factories, where replication proteins are properly assembled to form replication forks. Thus, recruitment of DNA replication origins to the replication factories must be the key step for the regulation of DNA replication. The transcription factor Runx1 associates with the nuclear matrix, the putative substructure of DNA replication factories. An earlier report from our laboratory showed that Runx1 activates polyomavirus DNA replication, and that this requires its nuclear matrix-binding activity. Here, we show that Runx1 activates polyomavirus DNA replication by stimulating the binding of the viral-encoded replication initiator/helicase, large T antigen, to its replication origin. We found that newly replicated polyomavirus DNA is associated with the nuclear matrix and that large T antigen is targeted to replication factories, suggesting that polyomavirus is replicated in replication factories on the nuclear matrix. Although Runx1 did not co-localize with large T antigen-containing foci by itself, it co-localized with large T antigen-containing replication factories during Runx1-dependent polyomavirus DNA replication. These observations together suggest that Runx1 recruits the polyomavirus replication origin to the replication factory on the nuclear matrix, and that this requires the nuclear matrix-binding activity of Runx1.
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. yota@virus.kyoto-u.ac.jp
authors.forename: Yota
authors.initials: Y
authors.lastname: Murakami
authors.forename: Ling-Feng
authors.initials: LF
authors.lastname: Chen
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sanechika
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Kohzaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D041681:NIH 3T3 Cells; D015530:Nuclear Matrix / Q000378:metabolism*; D011120:Polyomavirus / Q000235:genetics* / Q000502:physiology; D018741:Replication Origin; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000957:Antigens, Viral, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C493726:Runx1 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors